Publications by authors named "Shaorong Li"

29 Publications

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Dietary Inorganic Nitrate Protects Hepatic Ischemia-Reperfusion Injury Through NRF2-Mediated Antioxidative Stress.

Front Pharmacol 2021 7;12:634115. Epub 2021 Jun 7.

Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, China.

Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and liver transplantation and may cause hepatic impairment, resulting in acute liver dysfunction. Nitrate plays an important physiological regulatory role in the human body. Whether dietary nitrate could prevent HIRI is, however, unknown. A HIRI mouse model was established in that the blood supply to the median lobe and left lateral lobe was blocked for 60 min through the portal vein and related structures using an atraumatic clip. Sodium nitrate (4 mM) was administrated in advance through drinking water to compare the influence of sodium nitrate and normal water on HIRI. Liver necrosis and injury aggravated after HIRI. The group treated with sodium nitrate showed the lowest activities of plasma aminotransferase and lactate dehydrogenase and improved outcomes in histological investigation and TUNEL assay. Mechanistically, sodium nitrate intake increased plasma and liver nitric oxide levels, upregulated nuclear factor erythroid 2-related factor 2 (NRF2)-related molecules to reduce malondialdehyde level, and increased the activities of antioxidant enzymes to modulate hepatic oxidative stress. Dietary inorganic nitrate could prevent HIRI, possibly by activating the NRF2 pathway and modulating oxidative stress. Our study provides a novel therapeutic compound that could potentially prevent HIRI during liver transplantation or hepatic surgery.
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http://dx.doi.org/10.3389/fphar.2021.634115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215696PMC
June 2021

Aquaculture mediates global transmission of a viral pathogen to wild salmon.

Sci Adv 2021 May 26;7(22). Epub 2021 May 26.

Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Global expansion of aquaculture and agriculture facilitates disease emergence and catalyzes transmission to sympatric wildlife populations. The health of wild salmon stocks critically concerns Indigenous peoples, commercial and recreational fishers, and the general public. Despite potential impact of viral pathogens such as Piscine orthoreovirus-1 (PRV-1) on endangered wild salmon populations, their epidemiology in wild fish populations remains obscure, as does the role of aquaculture in global and local spread. Our phylogeographic analyses of PRV-1 suggest that development of Atlantic salmon aquaculture facilitated spread from Europe to the North and South East Pacific. Phylogenetic analysis and reverse transcription polymerase chain reaction surveillance further illuminate the circumstances of emergence of PRV-1 in the North East Pacific and provide strong evidence for Atlantic salmon aquaculture as a source of infection in wild Pacific salmon. PRV-1 is now an important infectious agent in critically endangered wild Pacific salmon populations, fueled by aquacultural transmission.
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http://dx.doi.org/10.1126/sciadv.abe2592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153721PMC
May 2021

Achromatic and wide-field metalens in the visible region.

Opt Express 2021 Apr;29(9):13542-13551

Optical metalens has been attracting more and more attention in recent years. To date, it is still difficult to simultaneously achieve wide field and broadband imaging in the visible region, which is very important in many applications, such as cameras, microscopy, and other imaging devices. In this paper, we design a double-layer metalens to achieve achromatic imaging over a field of view (FOV) of 60° in the visible light range of 470 nm to 650 nm, and its performance is verified by numerical simulations. The numerical aperture (NA) of the metalens is 0.61 and the average focusing efficiency is > 50% at normal incidence. The metalens has an additional advantage of polarization insensitivity.
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http://dx.doi.org/10.1364/OE.422126DOI Listing
April 2021

Infected juvenile salmon can experience increased predation during freshwater migration.

R Soc Open Sci 2021 Mar 24;8(3):201522. Epub 2021 Mar 24.

Pacific Salmon Ecology and Conservation Laboratory, Department of Forest and Conservation Sciences, University of British Columbia, Vancouver, Canada.

Predation risk for animal migrants can be impacted by physical condition. Although size- or condition-based selection is often observed, observing infection-based predation is rare due to the difficulties in assessing infectious agents in predated samples. We examined predation of outmigrating sockeye salmon () smolts by bull trout () in south-central British Columbia, Canada. We used a high-throughput quantitative polymerase chain reaction (qPCR) platform to screen for the presence of 17 infectious agents found in salmon and assess 14 host genes associated with viral responses. In one (2014) of the two years assessed (2014 and 2015), the presence of infectious haematopoietic necrosis virus (IHNv) resulted in 15-26 times greater chance of predation; in 2015 IHNv was absent among all samples, predated or not. Thus, we provide further evidence that infection can impact predation risk in migrants. Some smolts with high IHNv loads also exhibited gene expression profiles consistent with a virus-induced disease state. Nine other infectious agents were observed between the two years, none of which were associated with increased selection by bull trout. In 2014, richness of infectious agents was also associated with greater predation risk. This is a rare demonstration of predator consumption resulting in selection for prey that carry infectious agents. The mechanism by which this selection occurs is not yet determined. By culling infectious agents from migrant populations, fish predators could provide an ecological benefit to prey.
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http://dx.doi.org/10.1098/rsos.201522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074935PMC
March 2021

Discovery and surveillance of viruses from salmon in British Columbia using viral immune-response biomarkers, metatranscriptomics, and high-throughput RT-PCR.

Virus Evol 2021 Jan 1;7(1):veaa069. Epub 2020 Sep 1.

Pacific Biological Station, Fisheries and Oceans Canada, 3190 Hammond Bay Rd, Nanaimo, BC V9T 6N7, Canada.

The emergence of infectious agents poses a continual economic and environmental challenge to aquaculture production, yet the diversity, abundance, and epidemiology of aquatic viruses are poorly characterised. In this study, we applied salmon host transcriptional biomarkers to identify and select fish in a viral disease state, but only those that were negative for known viruses based on RT-PCR screening. These fish were selected for metatranscriptomic sequencing to discover potential viral pathogens of dead and dying farmed Atlantic () and Chinook () salmon in British Columbia (BC). We found that the application of the biomarker panel increased the probability of discovering viruses in aquaculture populations. We discovered two viruses that have not previously been characterised in Atlantic salmon farms in BC (Atlantic salmon calicivirus and Cutthroat trout virus-2), as well as partially sequenced three putative novel viruses. To determine the epidemiology of the newly discovered or emerging viruses, we conducted high-throughput reverse transcription polymerase chain reaction (RT-PCR) and screened over 9,000 farmed and wild salmon sampled over one decade. Atlantic salmon calicivirus and Cutthroat trout virus-2 were in more than half of the farmed Atlantic salmon we tested. Importantly we detected some of the viruses we first discovered in farmed Atlantic salmon in Chinook salmon, suggesting a broad host range. Finally, we applied hybridisation to determine infection and found differing cell tropism for each virus tested. Our study demonstrates that continual discovery and surveillance of emerging viruses in these ecologically important salmon will be vital for management of both aquaculture and wild resources in the future.
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http://dx.doi.org/10.1093/ve/veaa069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887441PMC
January 2021

Measures of diagnostic precision (repeatability and reproducibility) for three test methods designed to detect spring viremia of carp virus.

Prev Vet Med 2021 Mar 28;188:105288. Epub 2021 Jan 28.

Box 28, Group 30, RR2, Ste Anne, Manitoba, R5H 1R2, Canada. Electronic address:

Spring viremia of carp virus (SVCV) is a rhabdovirus of the Sprivivirus genus and the etiological agent of an internationally regulated aquatic animal disease in several fish species, including koi carp Cyprinus carpio L. The virus has a complex lifecycle with both acute and persistent stages of infection and can cause high mortality in affected populations. In this study, the diagnostic repeatability (within laboratory agreement) and reproducibility (between laboratory agreement) of 3 tests were investigated to assess their fitness as SVCV diagnostic tools. The tests, reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays targeting either the SVCV glycoprotein (Q1G) or nucleoprotein (Q2N) genes and virus isolation by cell culture (VI), were performed in a blinded study with four Canadian laboratories. Test panels consisted of duplicate sets of 100 tissue samples collected from 3 SVCV prevalence populations of koi: a low-prevalence negative reference population (n = 20 fish) as well as moderate- (n = 50 fish) and high-prevalence (n = 30 fish) populations of koi experimentally infected with SVCV. The Q1G and Q2N tests were performed with kidney tissue in 3 laboratories and with brain tissue in 1 laboratory whereas pools of kidney, spleen and gill tissues were tested with the VI assay in 2 laboratories. Agreement of binary results was evaluated using the observed proportion of agreement, Cohen's kappa and Gwet's agreement coefficient (AC1) whereas the concordance correlation coefficient (ccc) and Bland Altman's limit of agreement were used to evaluate agreement of the RT-qPCR continuous data. Gwet's AC1 provided a more stable estimate of agreement than Cohen's kappa. Overall, high repeatability (AC1, 0.78-0.90) and reproducibility (AC1, 0.74-0.89) were observed for the Q1G and Q2N tests when kidney tissue was used. Lower agreement estimates of repeatability (AC1, 0.54-0.77) and reproducibility (AC1, 0.50-0.80) were obtained for the VI test. RT-qPCR reproducibility was low with kidney-brain tissue pairs (AC1, 0.09-0.46) and high with inter-test pairs of brain (AC1, 0.76-0.86) or kidney tissue (0.75-0.86). Tissue-specific differences in virus load affected test precision and informed final tissue selection. Repeatability (ccc, 0.94-0.97) and reproducibility (ccc, 0.91-0.97) estimates of agreement for paired continuous data from the RT-qPCR assays were similarly high with kidney tissue and lower with paired brain (ccc, 0.15-0.83) and kidney-brain tissues (ccc, 0.01-0.55). The high precision of Q1G and Q2N with kidney tissue suggests that the tests are performing similarly and are suitable candidates for assessment of their diagnostic accuracy.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105288DOI Listing
March 2021

Environmental DNA from multiple pathogens is elevated near active Atlantic salmon farms.

Proc Biol Sci 2020 10 21;287(1937):20202010. Epub 2020 Oct 21.

Department of Ecology and Evolutionary Biology, University of Toronto, Ontario, Canada.

The spread of infection from reservoir host populations is a key mechanism for disease emergence and extinction risk and is a management concern for salmon aquaculture and fisheries. Using a quantitative environmental DNA methodology, we assessed pathogen environmental DNA in relation to salmon farms in coastal British Columbia, Canada, by testing for 39 species of salmon pathogens (viral, bacterial, and eukaryotic) in 134 marine environmental samples at 58 salmon farm sites (both active and inactive) over 3 years. Environmental DNA from 22 pathogen species was detected 496 times and species varied in their occurrence among years and sites, likely reflecting variation in environmental factors, other native host species, and strength of association with domesticated Atlantic salmon. Overall, we found that the probability of detecting pathogen environmental DNA (eDNA) was 2.72 (95% CI: 1.48, 5.02) times higher at active versus inactive salmon farm sites and 1.76 (95% CI: 1.28, 2.42) times higher per standard deviation increase in domesticated Atlantic salmon eDNA concentration at a site. If the distribution of pathogen eDNA accurately reflects the distribution of viable pathogens, our findings suggest that salmon farms serve as a potential reservoir for a number of infectious agents; thereby elevating the risk of exposure for wild salmon and other fish species that share the marine environment.
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http://dx.doi.org/10.1098/rspb.2020.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661312PMC
October 2020

How pathogens affect the marine habitat use and migration of sea trout (Salmo trutta) in two Norwegian fjord systems.

J Fish Dis 2020 Jul 4;43(7):729-746. Epub 2020 May 4.

NTNU University Museum, Norwegian University of Science and Technology, Trondheim, Norway.

Wild fish are confronting changing pathogen dynamics arising from anthropogenic disturbance and climate change. Pathogens can influence animal behaviour and life histories, yet there are little such data from fish in the high north where pathogen dynamics may differ from comparatively southern regions. We aimed to compare the pathogen communities of 160 wild anadromous brown trout in two fjords in northern Norway and to determine whether pathogens influenced area use or return to spawn. Application of high-throughput qPCR detected 11 of the 46 pathogens screened for; most frequently encountered were Ichthyobodo spp., Flavobacterium psychrophilum and Candidatus Branchiomonas cysticola. The rate of returning to freshwater during the spawning season was significantly lower for the Skjerstadfjord fish. Piscichlamydia salmonis and F. psychrophilum were indicator species for the Skjerstadfjord and pathogen communities in the two fjords differed according to perMANOVA. Individual length, Fulton's condition factor and the time between first and last detection of the fish were not related to the presence of pathogens ordinated using non-metric multidimensional scaling (NMDS). However, there was evidence that pathogen load was correlated with the expression of smoltification genes, which are upregulated by salmonids in freshwater. Correspondingly, percentage of time in freshwater after release was longer for fish with greater pathogen burdens.
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http://dx.doi.org/10.1111/jfd.13170DOI Listing
July 2020

A rapid intrinsic heart rate resetting response with thermal acclimation in rainbow trout, .

J Exp Biol 2020 06 15;223(Pt 12). Epub 2020 Jun 15.

Department of Zoology, University of British Columbia, Vancouver, BC, Canada, V6T 1Z4.

We examined cardiac pacemaker rate resetting in rainbow trout following a reciprocal temperature transfer. In the original experiment, performed in winter, 4°C-acclimated fish transferred to 12°C reset intrinsic heart rate after just 1 h (from 56.8±1.2 to 50.8±1.5 beats min); 12°C-acclimated fish transferred to 4°C reset intrinsic heart rate after 8 h (from 33.4±0.7 to 37.7±1.2 beats min). However, in a replicate experiment, performed in the summer using a different brood year, intrinsic heart rate was not reset, even after 10 weeks at a new temperature. Using this serendipitous opportunity, we compared mRNA expression changes of a suite of proteins in sinoatrial node (SAN), atrial and ventricular tissues after both 1 h and longer than 3 weeks for both experimental acclimation groups to identify those changes only associated with pacemaker rate resetting. Of the changes in mRNA expression occurring after more than 3 weeks of warm acclimation and associated with pacemaker rate resetting, we observed downregulation of in the atrium and ventricle, and upregulation of in the ventricle. However, in the SAN there were no mRNA expression changes unique to the fish with pacemaker rate resetting after either 1 h or 3 weeks of warm acclimation. Thus, despite identifying changes in mRNA expression of contractile cardiac tissues, there was an absence of changes in mRNA expression directly involved with the initial, rapid pacemaker rate resetting with warm acclimation. Importantly, pacemaker rate resetting with thermal acclimation does not always occur in rainbow trout.
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http://dx.doi.org/10.1242/jeb.215210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328139PMC
June 2020

Discovery and validation of candidate smoltification gene expression biomarkers across multiple species and ecotypes of Pacific salmonids.

Conserv Physiol 2019 11;7(1):coz051. Epub 2019 Oct 11.

Pacific Biological Station, Fisheries and Oceans Canada, Nanaimo, British Columbia, V9T 6N7, Canada.

Early marine survival of juvenile salmon is intimately associated with their physiological condition during smoltification and ocean entry. Smoltification (parr-smolt transformation) is a developmental process that allows salmon to acquire seawater tolerance in preparation for marine living. Traditionally, this developmental process has been monitored using gill Na/K-ATPase (NKA) activity or plasma hormones, but gill gene expression offers the possibility of another method. Here, we describe the discovery of candidate genes from gill tissue for staging smoltification using comparisons of microarray studies with particular focus on the commonalities between anadromous Rainbow trout and Sockeye salmon datasets, as well as a literature comparison encompassing more species. A subset of 37 candidate genes mainly from the microarray analyses was used for TaqMan quantitative PCR assay design and their expression patterns were validated using gill samples from four groups, representing three species and two ecotypes: Coho salmon, Sockeye salmon, stream-type Chinook salmon and ocean-type Chinook salmon. The best smoltification biomarkers, as measured by consistent changes across these four groups, were genes involved in ion regulation, oxygen transport and immunity. Smoltification gene expression patterns (using the top 10 biomarkers) were confirmed by significant correlations with NKA activity and were associated with changes in body brightness, caudal fin darkness and caudal peduncle length. We incorporate gene expression patterns of pre-smolt, smolt and de-smolt trials from acute seawater transfers from a companion study to develop a preliminary seawater tolerance classification model for ocean-type Chinook salmon. This work demonstrates the potential of gene expression biomarkers to stage smoltification and classify juveniles as pre-smolt, smolt or de-smolt.
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http://dx.doi.org/10.1093/conphys/coz051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788492PMC
October 2019

Endangered wild salmon infected by newly discovered viruses.

Elife 2019 09 3;8. Epub 2019 Sep 3.

Department of Earth, Ocean and Atmospheric Sciences, University of British Columbia, Vancouver, Canada.

The collapse of iconic, keystone populations of sockeye () and Chinook () salmon in the Northeast Pacific is of great concern. It is thought that infectious disease may contribute to declines, but little is known about viruses endemic to Pacific salmon. Metatranscriptomic sequencing and surveillance of dead and moribund cultured Chinook salmon revealed a novel arenavirus, reovirus and nidovirus. Sequencing revealed two different arenavirus variants which each infect wild Chinook and sockeye salmon. In situ hybridisation localised arenavirus mostly to blood cells. Population surveys of >6000 wild juvenile Chinook and sockeye salmon showed divergent distributions of viruses, implying different epidemiological processes. The discovery in dead and dying farmed salmon of previously unrecognised viruses that are also widely distributed in wild salmon, emphasizes the potential role that viral disease may play in the population dynamics of wild fish stocks, and the threat that these viruses may pose to aquaculture.
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http://dx.doi.org/10.7554/eLife.47615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721791PMC
September 2019

Cumulative Effects of Thermal and Fisheries Stressors Reveal Sex-Specific Effects on Infection Development and Early Mortality of Adult Coho Salmon ().

Physiol Biochem Zool 2019 Sep/Oct;92(5):505-529

Multiple stressors are commonly encountered by wild animals, but their cumulative effects are poorly understood, especially regarding infection development. We conducted a holding study with repeated gill and blood sampling to characterize the effects of cumulative stressors on infection development in adult coho salmon. Treatments included chronic thermal stress (15°C vs. 10°C) and acute gill net entanglement with an air exposure (simulating fisheries bycatch release). The potential loadings of 35 infectious agents and the expression of 17 host immune genes were quantified using high-throughput quantitative polymerase chain reaction, while host physiology was characterized with chemical analysis of blood. Temporal increases in infectious agent richness and loads were concurrent with decreased expression of immune genes in fish sampled in the river. In the laboratory, mortality was minimal in cool water regardless of fishery treatment (<15%). Elevated water temperature under laboratory conditions increased mortality of males and females (8% and 28% mortality, respectively, delayed by >1 wk) and enhanced mortality associated with handling and biopsy (∼40% both sexes). Experimental gillnetting at high temperature further enhanced female mortality (73%). Fish held at high temperature demonstrated heavier infectious agent loads, osmoregulatory impairment, suppressed female maturation, and upregulation of inflammatory and extracellular immune genes. At high temperature, heavy loads were associated with premature mortality. Females exhibited physiological impairment from both stressors after 1 wk, and infection burdens correlated poorly with immune gene regulation compared with males. Cumulative effects of multiple stressors on female mortality are likely a function of physiological impairment and enhanced infections at high temperature.
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http://dx.doi.org/10.1086/705125DOI Listing
January 2020

Salmonid gene expression biomarkers indicative of physiological responses to changes in salinity and temperature, but not dissolved oxygen.

J Exp Biol 2019 07 5;222(Pt 13). Epub 2019 Jul 5.

Pacific Biological Station, Fisheries and Oceans Canada, Nanaimo, BC, Canada, V9T 6N7

An organism's ability to respond effectively to environmental change is critical to its survival. Yet, life stage and overall condition can dictate tolerance thresholds to heightened environmental stressors, such that stress may not be equally felt across individuals and at all times. Also, the transcriptional responses induced by environmental changes can reflect both generalized responses as well as others that are highly specific to the type of change being experienced. Thus, if transcriptional biomarkers specific to a stressor, even under multi-stressor conditions, can be identified, the biomarkers could then be applied in natural environments to determine when and where an individual experiences such a stressor. Here, we experimentally challenged juvenile Chinook salmon () to validate candidate gill gene expression biomarkers. A sophisticated experimental design manipulated salinity (freshwater, brackish water and seawater), temperature (10, 14 and 18°C) and dissolved oxygen (normoxia and hypoxia) in all 18 possible combinations for 6 days using separate trials for three smolt statuses (pre-smolt, smolt and de-smolt). In addition, changes in juvenile behaviour, plasma variables, gill Na/K-ATPase activity, body size, body morphology and skin pigmentation supplemented the gene expression responses. We identified biomarkers specific to salinity and temperature that transcended the multiple stressors, smolt status and mortality (live, dead and moribund). Similar biomarkers for dissolved oxygen were not identified. This work demonstrates the unique power of gene expression biomarkers to identify a specific stressor even under multi-stressor conditions, and we discuss our next steps for hypoxia biomarkers using an RNA-seq study.
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http://dx.doi.org/10.1242/jeb.198036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6633282PMC
July 2019

Distribution and Phylogeny of Erythrocytic Necrosis Virus (ENV) in Salmon Suggests Marine Origin.

Viruses 2019 04 18;11(4). Epub 2019 Apr 18.

Department of Earth, Ocean and Atmospheric Sciences, University of British Columbia, 2207 Main Mall, Vancouver, BC V6T 1Z4, Canada.

Viral erythrocytic necrosis (VEN) affects over 20 species of marine and anadromous fishes in the North Atlantic and North Pacific Oceans. However, the distribution and strain variation of its viral causative agent, erythrocytic necrosis virus (ENV), has not been well characterized within Pacific salmon. Here, metatranscriptomic sequencing of Chinook salmon revealed that ENV infecting salmon was closely related to ENV from Pacific herring, with inferred amino-acid sequences from Chinook salmon being 99% identical to those reported for herring. Sequence analysis also revealed 89 protein-encoding sequences attributed to ENV, greatly expanding the amount of genetic information available for this virus. High-throughput PCR of over 19,000 fish showed that ENV is widely distributed in the NE Pacific Ocean and was detected in 12 of 16 tested species, including in 27% of herring, 38% of anchovy, 17% of pollock, and 13% of sand lance. Despite frequent detection in marine fish, ENV prevalence was significantly lower in fish from freshwater (0.03%), as assessed with a generalized linear mixed effects model ( = 5.5 × 10). Thus, marine fish are likely a reservoir for the virus. High genetic similarity between ENV obtained from salmon and herring also suggests that transmission between these hosts is likely.
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http://dx.doi.org/10.3390/v11040358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520742PMC
April 2019

Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer.

Oncol Rep 2019 Jan 17;41(1):77-86. Epub 2018 Oct 17.

Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, Shandong 250117, P.R. China.

Osimertinib (AZD9291) is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated significant clinical benefits in patients with EGFR‑sensitizing mutations or the T790M mutation. However, the potential therapeutic effect of osimertinib combined with ionizing irradiation (IR) is not well understood. The present study investigated treatment with osimertinib combined with IR in EGFR T790M non‑small cell lung cancer (NCI‑H1975) in vitro and in vivo. The results revealed that osimertinib inhibited proliferation and clonogenic survival following irradiation, decreased G2/M phase arrest in irradiated cells, and delayed DNA damage repair in a concentration‑ and time‑dependent manner. Furthermore, osimertinib alone or in combination with IR, blocked the phosphorylation of EGFR (Tyr1068/Tyr1173), protein kinase B and extracellular signal‑regulated kinase. Osimertinib also enhanced the antitumor activity of IR in tumor‑bearing nude mice. The results of the present study indicated that osimertinib has therapeutic potential as a radiation‑sensitizer in lung cancer cells harboring the EGFR T790M mutation, providing a rationale for clinically combining osimertinib with irradiation in EGFR T790M non‑small cell lung cancer.
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http://dx.doi.org/10.3892/or.2018.6803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278463PMC
January 2019

Developing specific molecular biomarkers for thermal stress in salmonids.

BMC Genomics 2018 Oct 16;19(1):749. Epub 2018 Oct 16.

Fisheries and Oceans Canada, Pacific Biological Station, 3190 Hammond Bay Road, Nanaimo, BC, V9T 6N7, Canada.

Background: Pacific salmon (Oncorhynchus spp.) serve as good biological indicators of the breadth of climate warming effects on fish because their anadromous life cycle exposes them to environmental challenges in both marine and freshwater environments. Our study sought to mine the extensive functional genomic studies in fishes to identify robust thermally-responsive biomarkers that could monitor molecular physiological signatures of chronic thermal stress in fish using non-lethal sampling of gill tissue.

Results: Candidate thermal stress biomarkers for gill tissue were identified using comparisons among microarray datasets produced in the Molecular Genetics Laboratory, Pacific Biological Station, Nanaimo, BC, six external, published microarray studies on chronic and acute temperature stress in salmon, and a comparison of significant genes across published studies in multiple fishes using deep literature mining. Eighty-two microarray features related to 39 unique gene IDs were selected as candidate chronic thermal stress biomarkers. Most of these genes were identified both in the meta-analysis of salmon microarray data and in the literature mining for thermal stress markers in salmonids and other fishes. Quantitative reverse transcription PCR (qRT-PCR) assays for 32 unique genes with good efficiencies across salmon species were developed, and their activity in response to thermally challenged sockeye salmon (O. nerka) and Chinook salmon (O. tshawytscha) (cool, 13-14 °C and warm temperatures 18-19 °C) over 5-7 days was assessed. Eight genes, including two transcripts of each SERPINH1 and HSP90AA1, FKBP10, MAP3K14, SFRS2, and EEF2 showed strong and robust chronic temperature stress response consistently in the discovery analysis and both sockeye and Chinook salmon validation studies.

Conclusions: The results of both discovery analysis and gene expression showed that a panel of genes involved in chaperoning and protein rescue, oxidative stress, and protein biosynthesis were differentially activated in gill tissue of Pacific salmon in response to elevated temperatures. While individually, some of these biomarkers may also respond to other stressors or biological processes, when expressed in concert, we argue that a biomarker panel comprised of some or all of these genes could provide a reliable means to specifically detect thermal stress in field-caught salmon.
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http://dx.doi.org/10.1186/s12864-018-5108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192343PMC
October 2018

Human Activity Determines the Presence of Integron-Associated and Antibiotic Resistance Genes in Southwestern British Columbia.

Front Microbiol 2018 1;9:852. Epub 2018 May 1.

Department of Pathology & Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.

The dissemination of antibiotic resistant bacteria from anthropogenic sources into the environment poses an emerging public health threat. Antibiotic resistance genes (ARGs) and gene-capturing systems such as integron-associated integrase genes () play a key role in alterations of microbial communities and the spread of antibiotic resistant bacteria into the environment. In order to assess the effect of anthropogenic activities on watersheds in southwestern British Columbia, the presence of putative antibiotic resistance and integrase genes was analyzed in the microbiome of agricultural, urban influenced, and protected watersheds. A metagenomics approach and high-throughput quantitative PCR (HT qPCR) were used to screen for elements of resistance including ARGs and . Metagenomic sequencing of bacterial genomic DNA was used to characterize the resistome of microbial communities present in watersheds over a 1-year period. There was a low prevalence of ARGs relative to the microbial population (<1%). Analysis of the metagenomic sequences detected a total of 60 elements of resistance including 46 ARGs, , and groEL/ genes and 12 quaternary ammonium compounds () resistance genes across all watershed locations. The relative abundance and richness of ARGs was found to be highest in agriculture impacted watersheds compared to urban and protected watersheds. A downstream transport pattern was observed in the impacted watersheds (urban and agricultural) during dry months. Similar to other reports, this study found a strong association between and ARGs (e.g., ), an association which may be used as a proxy for anthropogenic activities. Chemical analysis of water samples for three major groups of antibiotics was below the detection limit. However, the high richness and gene copy numbers (GCNs) of ARGs in impacted sites suggest that the effects of effluents on microbial communities are occurring even at low concentrations of antimicrobials in the water column. Antibiotic resistance and integrase genes in a year-long metagenomic study showed that ARGs were driven mainly by environmental factors from anthropogenized sites in agriculture and urban watersheds. Environmental factors such as land-use and water quality parameters accounted for 45% of the variability observed in watershed locations.
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http://dx.doi.org/10.3389/fmicb.2018.00852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938356PMC
May 2018

Distinct seasonal infectious agent profiles in life-history variants of juvenile Fraser River Chinook salmon: An application of high-throughput genomic screening.

PLoS One 2018 19;13(4):e0195472. Epub 2018 Apr 19.

Fisheries and Oceans Canada, Nanaimo, BC, Canada.

Disease-causing infectious agents are natural components of ecosystems and considered a major selective force driving the evolution of host species. However, knowledge of the presence and abundance of suites of infectious agents in wild populations has been constrained by our ability to easily screen for them. Using salmon as a model, we contrasted seasonal pathogenic infectious agents in life history variants of juvenile Chinook salmon from the Fraser River system (N = 655), British Columbia (BC), through the application of a novel high-throughput quantitative PCR monitoring platform. This included freshwater hatchery origin fish and samples taken at sea between ocean entry in spring and over-winter residence in coastal waters. These variants currently display opposite trends in productivity, with yearling stocks generally in decline and sub-yearling stocks doing comparatively well. We detected the presence of 32 agents, 21 of which were at >1% prevalence. Variants carried a different infectious agent profile in terms of (1) diversity, (2) origin or transmission environment of infectious agents, and (3) prevalence and abundance of individual agents. Differences in profiles tended to reflect differential timing and residence patterns through freshwater, estuarine and marine habitats. Over all seasons, individual salmon carried an average of 3.7 agents. Diversity changed significantly, increasing upon saltwater entrance, increasing through the fall and decreasing slightly in winter. Diversity varied between life history types with yearling individuals carrying 1.3-times more agents on average. Shifts in prevalence and load over time were examined to identify agents with the greatest potential for impact at the stock level; those displaying concurrent decrease in prevalence and load truncation with time. Of those six that had similar patterns in both variants, five reached higher prevalence in yearling fish while only one reached higher prevalence in sub-yearling fish; this pattern was present for an additional five agents in yearling fish only.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195472PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908190PMC
July 2018

The evaluation of E. faecalis colonies dissolution ability of sodium hypochlorite in microenvironment by a novel device.

Biomed Microdevices 2018 04 12;20(2):36. Epub 2018 Apr 12.

The Department of Endodontics, School of Stomatology, Capital Medical University, Beijing, China.

Enterococcus faecalis(E. faecalis) is a common microorganism could be isolated from the infected canals, especially in the case of refractory apical periodontitis. Due to its ability to invade the dentinal tubules and highly resistant to antimicrobial strategies, the thorough debridement of E.faecalis is hard to achieve. And that may be one of the reasons to cause reinfection and therapeutic failure. According to the anatomy of dentinal tubules published before and the results of our team previous work, we designed six types of microtubes with different sizes. By using the method of centrifugation and incubation, a standard infected model mimicking dentinal tubules was established. Sodium hypochlorite (NaClO) is the most popular irrigant applied in root canal treatment. We used three different concentrations with four distinct irrigation duration to observe the antibacterial process of E. faecalis colonies within microtubes dynamically. We concluded that the role of NaClO in the microtubes is concentration dependent and duration dependent. And the interpretation of the results has a certain reference value for clinicians.
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http://dx.doi.org/10.1007/s10544-018-0279-3DOI Listing
April 2018

Molecular indices of viral disease development in wild migrating salmon.

Conserv Physiol 2017 27;5(1):cox036. Epub 2017 Jun 27.

Fisheries and Oceans Canada, Pacific Biological Station, 3190 Hammond Bay Road, Nanaimo, British Columbia, Canada V9T 6N7.

Infectious diseases can impact the physiological performance of individuals, including their mobility, visual acuity, behavior and tolerance and ability to effectively respond to additional stressors. These physiological effects can influence competitiveness, social hierarchy, habitat usage, migratory behavior and risk to predation, and in some circumstances, viability of populations. While there are multiple means of detecting infectious agents (microscopy, culture, molecular assays), the detection of infectious diseases in wild populations in circumstances where mortality is not observable can be difficult. Moreover, if infection-related physiological compromise leaves individuals vulnerable to predation, it may be rare to observe wildlife in a late stage of disease. Diagnostic technologies designed to diagnose cause of death are not always sensitive enough to detect early stages of disease development in live-sampled organisms. Sensitive technologies that can differentiate agent carrier states from active disease states are required to demonstrate impacts of infectious diseases in wild populations. We present the discovery and validation of salmon host transcriptional biomarkers capable of distinguishing fish in an active viral disease state [viral disease development (VDD)] from those carrying a latent viral infection, and viral versus bacterial disease states. Biomarker discovery was conducted through meta-analysis of published and in-house microarray data, and validation performed on independent datasets including disease challenge studies and farmed salmon diagnosed with various viral, bacterial and parasitic diseases. We demonstrate that the VDD biomarker panel is predictive of disease development across RNA-viral species, salmon species and salmon tissues, and can recognize a viral disease state in wild-migrating salmon. Moreover, we show that there is considerable overlap in the biomarkers resolved in our study in salmon with those based on similar human viral influenza research, suggesting a highly conserved suite of host genes associated with viral disease that may be applicable across a broad range of vertebrate taxa.
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http://dx.doi.org/10.1093/conphys/cox036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499884PMC
June 2017

Heart and skeletal muscle inflammation (HSMI) disease diagnosed on a British Columbia salmon farm through a longitudinal farm study.

PLoS One 2017 22;12(2):e0171471. Epub 2017 Feb 22.

Pacific Biological Station, Fisheries and Oceans Canada, Nanaimo, British Columbia, Canada.

Heart and skeletal muscle inflammation (HSMI) is an emerging disease of marine-farmed Atlantic Salmon (Salmo salar), first recognized in 1999 in Norway, and later also reported in Scotland and Chile. We undertook a longitudinal study involving health evaluation over an entire marine production cycle on one salmon farm in British Columbia (Canada). In previous production cycles at this farm site and others in the vicinity, cardiac lesions not linked to a specific infectious agent or disease were identified. Histologic assessments of both live and moribund fish samples collected at the farm during the longitudinal study documented at the population level the development, peak, and recovery phases of HSMI. The fish underwent histopathological evaluation of all tissues, Twort's Gram staining, immunohistochemistry, and molecular quantification in heart tissue of 44 agents known or suspected to cause disease in salmon. Our analysis showed evidence of HSMI histopathological lesions over an 11-month timespan, with the prevalence of lesions peaking at 80-100% in sampled fish, despite mild clinical signs with no associated elevation in mortalities reported at the farm level. Diffuse mononuclear inflammation and myodegeneration, consistent with HSMI, was the predominant histologic observation in affected heart and skeletal muscle. Infective agent monitoring identified three agents at high prevalence in salmon heart tissue, including Piscine orthoreovirus (PRV), and parasites Paranucleospora theridion and Kudoa thyrsites. However, PRV alone was statistically correlated with the occurrence and severity of histopathological lesions in the heart. Immunohistochemical staining further localized PRV throughout HSMI development, with the virus found mainly within red blood cells in early cases, moving into the cardiomyocytes within or, more often, on the periphery of the inflammatory reaction during the peak disease, and reducing to low or undetectable levels later in the production cycle. This study represents the first longitudinal assessment of HSMI in a salmon farm in British Columbia, providing new insights on the pathogenesis of the disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171471PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321275PMC
August 2017

Enhanced light absorption in thin film silicon solar cells with Fourier-series based periodic nanostructures.

Opt Express 2016 Jan;24(2):A408-13

We proposed a Fourier-series based periodic nanostructure(FSPN) for light trapping in thin film silicon solar cells. By globally optimizing the Fourier coefficients across entire silicon absorption spectrum, we obtained a FSPN structure with short circuit current density greater than 24 mA/cm(2) for a 1μm real silicon absorption layer. The spectral analysis shows at normal incidence the FSPN exhibits a collection effect of periodic gratings and performs over 84.6% better than random texture. The angular analysis shows that the FSPN outperforms grating and random textures within 70 °.
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http://dx.doi.org/10.1364/OE.24.00A408DOI Listing
January 2016

Are capecitabine and the active metabolite 5-Fu CNS penetrable to treat breast cancer brain metastasis?

Drug Metab Dispos 2015 Mar 29;43(3):411-7. Epub 2014 Dec 29.

Drug Metabolism and Pharmacokinetics, Innovation Center China, Innovative Medicine and Early Development, AstraZeneca, Shanghai, China (J.Z., L.Z, Y.Y., S.L., Z.C.); Bioscience, Innovation Center China, Innovative Medicine and Early Development, AstraZeneca, Shanghai, China (L.X., J.L., X.Z., Y.B.); and Chemistry, Innovation Center China, Innovative Medicine and Early Development, AstraZeneca, Shanghai, China (W.Z.)

Brain metastasis (BM) is increasingly diagnosed in Her2 positive breast cancer (BC) patients. Lack of effective treatment to breast cancer brain metastases (BCBMs) is probably due to inability of the current therapeutic agents to cross the blood-brain barrier. The central nervous system (CNS) response rate in BCBM patients was reported to improve from 2.6%-6% (lapatinib) to 20%-65% (lapatinib in combination with capecitabine). Lapatinib is a poor brain penetrant. In this study, we evaluated the CNS penetration of capecitabine and hoped to interpret the mechanism of the improved CNS response from the pharmacokinetic (PK) perspective. Capecitabine does not have antiproliferative activity and 5-fluorouracil (5-FU) is the active metabolite. Capecitabine was orally administered to mouse returning an unbound brain-to-blood ratio (Kp,uu,brain) at 0.13 and cerebrospinal fluid (CSF)-to-unbound blood ratio (Kp,uu,CSF) at 0.29 for 5-FU. Neither free brain nor CSF concentration of 5-FU can achieve antiproliferative concentration for 50% of maximal inhibition of cell proliferation of 4.57 µM. BCBM mice were treated with capecitabine monotherapy or in combination with lapatinib. The Kp,uu,brain value of 5-FU increased to 0.17 in the brain tumor in the presence of lapatinib, which is still far below unity. The calculated free concentration of 5-FU and lapatinib in the brain tumor did not reach the antiproliferative potency and neither treatment showed antitumor activity in the BCBM mice. The CNS penetration of 5-FU in human was predicted based on the penetration in preclinical brain tumor, CSF, and human PK and the predicted free CNS concentration was below the antiproliferative potency. These results suggest that CNS penetration of 5-FU and lapatinib are not desirable and development of a true CNS penetrable therapeutic agent will further improve the response rate for BCBM.
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http://dx.doi.org/10.1124/dmd.114.061820DOI Listing
March 2015

Infectious disease, shifting climates, and opportunistic predators: cumulative factors potentially impacting wild salmon declines.

Evol Appl 2014 Aug 27;7(7):812-55. Epub 2014 May 27.

Forest and Conservation Sciences, University of British Columbia Vancouver, BC, Canada.

Emerging diseases are impacting animals under high-density culture, yet few studies assess their importance to wild populations. Microparasites selected for enhanced virulence in culture settings should be less successful maintaining infectivity in wild populations, as once the host dies, there are limited opportunities to infect new individuals. Instead, moderately virulent microparasites persisting for long periods across multiple environments are of greatest concern. Evolved resistance to endemic microparasites may reduce susceptibilities, but as barriers to microparasite distributions are weakened, and environments become more stressful, unexposed populations may be impacted and pathogenicity enhanced. We provide an overview of the evolutionary and ecological impacts of infectious diseases in wild salmon and suggest ways in which modern technologies can elucidate the microparasites of greatest potential import. We present four case studies that resolve microparasite impacts on adult salmon migration success, impact of river warming on microparasite replication, and infection status on susceptibility to predation. Future health of wild salmon must be considered in a holistic context that includes the cumulative or synergistic impacts of multiple stressors. These approaches will identify populations at greatest risk, critically needed to manage and potentially ameliorate the shifts in current or future trajectories of wild populations.
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http://dx.doi.org/10.1111/eva.12164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227861PMC
August 2014

Immune response genes and pathogen presence predict migration survival in wild salmon smolts.

Mol Ecol 2014 Dec 21;23(23):5803-15. Epub 2014 Nov 21.

Department of Forest and Conservation Sciences, Faculty of Forestry, University of British Columbia, 2424 Main Mall, Vancouver, BC, V6T 1Z4, Canada.

We present the first data to link physiological responses and pathogen presence with subsequent fate during migration of wild salmonid smolts. We tagged and non-lethally sampled gill tissue from sockeye salmon (Oncorhynchus nerka) smolts as they left their nursery lake (Chilko Lake, BC, Canada) to compare gene expression profiles and freshwater pathogen loads with migration success over the first ~1150 km of their migration to the North Pacific Ocean using acoustic telemetry. Fifteen per cent of smolts were never detected again after release, and these fish had gene expression profiles consistent with an immune response to one or more viral pathogens compared with fish that survived their freshwater migration. Among the significantly upregulated genes of the fish that were never detected postrelease were MX (interferon-induced GTP-binding protein Mx) and STAT1 (signal transducer and activator of transcription 1-alpha/beta), which are characteristic of a type I interferon response to viral pathogens. The most commonly detected pathogen in the smolts leaving the nursery lake was infectious haematopoietic necrosis virus (IHNV). Collectively, these data show that some of the fish assumed to have died after leaving the nursery lake appeared to be responding to one or more viral pathogens and had elevated stress levels that could have contributed to some of the mortality shortly after release. We present the first evidence that changes in gene expression may be predictive of some of the freshwater migration mortality in wild salmonid smolts.
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http://dx.doi.org/10.1111/mec.12980DOI Listing
December 2014

Consequences of high temperatures and premature mortality on the transcriptome and blood physiology of wild adult sockeye salmon (Oncorhynchus nerka).

Ecol Evol 2012 Jul;2(7):1747-64

Elevated river water temperature in the Fraser River, British Columbia, Canada, has been associated with enhanced mortality of adult sockeye salmon (Oncorhynchus nerka) during their upriver migration to spawning grounds. We undertook a study to assess the effects of elevated water temperatures on the gill transcriptome and blood plasma variables in wild-caught sockeye salmon. Naturally migrating sockeye salmon returning to the Fraser River were collected and held at ecologically relevant temperatures of 14°C and 19°C for seven days, a period representing a significant portion of their upstream migration. After seven days, sockeye salmon held at 19°C stimulated heat shock response genes as well as many genes associated with an immune response when compared with fish held at 14°C. Additionally, fish at 19°C had elevated plasma chloride and lactate, suggestive of a disturbance in osmoregulatory homeostasis and a stress response detectable in the blood plasma. Fish that died prematurely over the course of the holding study were compared with time-matched surviving fish; the former fish were characterized by an upregulation of several transcription factors associated with apoptosis and downregulation of genes involved in immune function and antioxidant activity. Ornithine decarboxylase (ODC1) was the most significantly upregulated gene in dying salmon, which suggests an association with cellular apoptosis. We hypothesize that the observed decrease in plasma ions and increases in plasma cortisol that occur in dying fish may be linked to the increase in ODC1. By highlighting these underlying physiological mechanisms, this study enhances our understanding of the processes involved in premature mortality and temperature stress in Pacific salmon during migration to spawning grounds.
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http://dx.doi.org/10.1002/ece3.274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434914PMC
July 2012

Genomic signatures predict migration and spawning failure in wild Canadian salmon.

Science 2011 Jan;331(6014):214-7

Molecular Genetics Section, Pacific Biological Station, 3190 Hammond Bay Road, Fisheries and Oceans Canada, Nanaimo, BC V9T 6N7, Canada.

Long-term population viability of Fraser River sockeye salmon (Oncorhynchus nerka) is threatened by unusually high levels of mortality as they swim to their spawning areas before they spawn. Functional genomic studies on biopsied gill tissue from tagged wild adults that were tracked through ocean and river environments revealed physiological profiles predictive of successful migration and spawning. We identified a common genomic profile that was correlated with survival in each study. In ocean-tagged fish, a mortality-related genomic signature was associated with a 13.5-fold greater chance of dying en route. In river-tagged fish, the same genomic signature was associated with a 50% increase in mortality before reaching the spawning grounds in one of three stocks tested. At the spawning grounds, the same signature was associated with 3.7-fold greater odds of dying without spawning. Functional analysis raises the possibility that the mortality-related signature reflects a viral infection.
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http://dx.doi.org/10.1126/science.1196901DOI Listing
January 2011

Salmon spawning migration: metabolic shifts and environmental triggers.

Comp Biochem Physiol Part D Genomics Proteomics 2009 Jun 6;4(2):75-89. Epub 2008 Dec 6.

Molecular Genetics Section, Pacific Biological Station, 3190 Hammond Bay Road, Fisheries and Oceans Canada, Nanaimo, BC, Canada V9T 6N7.

A large-scale functional genomics study revealed shifting metabolic processes in white muscle during the final 1300 km migration of wild sockeye salmon to their spawning grounds in the Fraser River, British Columbia. In 2006, Lower Adams stock sockeye salmon ceased feeding after passing the Queen Charlotte Islands, 850 km from the Fraser River. Enhanced protein turnover and reduced transcription of actin, muscle contractile and heme-related proteins were early starvation responses in saltwater. Arrival to the estuarine environment triggered massive protein turnover through induction of proteasomal and lysosomal proteolysis and protein biosynthesis, and a shift from anaerobic glycolysis to oxidative phosphorylation. Response to entry into freshwater was modest, with up-regulation of heat shock proteins and nitric oxide biosynthesis. High river temperatures resulted in a strong defense/immune response and high mortalities in 50% of fish. Arrival to the spawning grounds triggered further up-regulation of oxidative phosphorylation and proteolysis, down-regulation of protein biosynthesis and helicase activity, and continued down-regulation of muscle proteins and most glycolytic enzymes. However, sharp up-regulation of PFK-I indicated induction of glycolytic potential at the spawning grounds. The identification of potential environmental cues triggering genome-wide transcriptional shifts in white muscle associated with migration and the strong activation of proteasomal proteolysis were both novel findings.
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http://dx.doi.org/10.1016/j.cbd.2008.11.002DOI Listing
June 2009

The salmonid MHC class I: more ancient loci uncovered.

Immunogenetics 2006 Jul 23;58(7):571-89. Epub 2006 Jun 23.

Pacific Biological Station, Fisheries and Oceans, Canada, 3190 Hammond Bay Rd., Nanaimo, B.C. V9T 6N7, Canada.

An unprecedented level of sequence diversity has been maintained in the salmonid major histocompatibility complex (MHC) class I UBA gene, with between lineage AA sequence identities as low as 34%. The derivation of deep allelic lineages may have occurred through interlocus exon shuffling or convergence of ancient loci with the UBA locus, but until recently, no such ancient loci were uncovered. Herein, we document the existence of eight additional MHC class I loci in salmon (UCA, UDA, UEA, UFA, UGA, UHA, ULA, and ZE), six of which share exon 2 and 3 lineages with UBA, and three of which have not been described elsewhere. Half of the UBA exon 2 lineages and all UBA exon 3 lineages are shared with other loci. Two loci, UGA and UEA, share only a single exon lineage with UBA, likely generated through exon shuffling. Based on sequence homologies, we hypothesize that most exchanges and duplications occurred before or during tetraploidization (50 to 100 Ma). Novel loci that share no relationship with other salmonid loci are also identified (UHA and ZE). Each locus is evaluated for its potential to function as a class Ia gene based on gene expression, conserved residues and polymorphism. UBA is the only locus that can indisputably be classified as a class Ia gene, although three of the eight loci (ZE, UCA, and ULA) conform in three out of four measures. We hypothesize that these additional loci are in varying states of degradation to class Ib genes.
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http://dx.doi.org/10.1007/s00251-006-0125-2DOI Listing
July 2006