Chromosomal aberrations and early mortality in a non-mammalian vertebrate: example from pressure-induced triploid Atlantic salmon.

In commercial aquaculture, the production of triploid fish is currently the most practical approach to prevent maturation and farm-to-wild introgression following escapes. However, triploids often exhibit poor welfare, and the underlying mechanisms remain unclear. Inheritance issues associated with sub-optimal hydrostatic pressure treatments used to induce triploidy, or the genetic background of parental fish, have been speculated to contribute. We tested this by quantifying the frequency and type of chromosomal aberrations in Atlantic salmon subjected to a gradient of sub-optimal pressure treatments (Experiment 1) and from multiple mothers (Experiment 2). From these experiments, we genotyped a subsample of ~900 eyed eggs and all ~3300 surviving parr across ~20 microsatellites. In contrast to the low frequency of chromosomal aberrations in the diploid (no hydrostatic pressure) and triploid (full 9500 PSI treatment) controls, eyed eggs subjected to sub-optimal pressure treatments (6500-8500 PSI) had a higher incidence of chromosomal aberrations such as aneuploidy and uniparental disomy, corresponding to lower triploidization success and higher egg mortality rates. We also observed maternal effects on triploidization success and incidence of chromosomal aberrations, with certain half-sibling families exhibiting more aberrations than others. Chromosomal aberrations were rare among surviving parr, suggesting a purge of maladapted individuals during early development. This study demonstrates that sub-optimal hydrostatic pressure treatments and maternal effects not only influence the success of triploidization treatments, but may also affect the incidence of chromosomal aberrations and early mortality. The results have important implications for aquaculture breeding programs and their efforts to prevent farm-to-wild introgression.

Most of the escaped farmed salmon entering a river during a 5-year period were infected with one or more viruses.

Disease interactions between farmed and wild populations have been poorly documented for most aquaculture species, in part due to the complexities to study this. Here, we tested 567 farmed Atlantic salmon escapees, captured in a Norwegian river during 2014-2018, for five viral infections that are prevalent in global salmonid aquaculture. Over 90% of the escapees were infected with one or more viruses. Overall prevalences were: 75.7% for piscine orthoreovirus (PRV-1), 43.6% for salmonid alphavirus (SAV), 31.2% for piscine myocarditis virus (PMCV), 1.2% for infectious pancreatic necrosis virus (IPNV) and 0.4% for salmon anaemia virus (ISAV). A significantly higher prevalence of PMCV infection was observed in immature compared to mature individuals. The prevalence of both SAV and PMCV infections was higher in fish determined by fatty acid profiling to be 'recent' as opposed to 'early' escapees that had been in the wild for a longer period of time. This is the first study to establish a time-series of viral infection status of escapees entering a river with a native salmon population. Our results demonstrate that farmed escapees represent a continuous source of infectious agents which could potentially be transmitted to wild fish populations.

Epistatic regulation of growth in Atlantic salmon revealed: a QTL study performed on the domesticated-wild interface.

BACKGROUND: Quantitative traits are typically considered to be under additive genetic control. Although there are indications that non-additive factors have the potential to contribute to trait variation, experimental demonstration remains scarce. Here, we investigated the genetic basis of growth in Atlantic salmon by exploiting the high level of genetic diversity and trait expression among domesticated, hybrid and wild populations. RESULTS: After rearing fish in common-garden experiments under aquaculture conditions, we performed a variance component analysis in four mapping populations totaling ~ 7000 individuals from six wild, two domesticated and three F1 wild/domesticated hybrid strains. Across the four independent datasets, genome-wide significant quantitative trait loci (QTLs) associated with weight and length were detected on a total of 18 chromosomes, reflecting the polygenic nature of growth. Significant QTLs correlated with both length and weight were detected on chromosomes 2, 6 and 9 in multiple datasets. Significantly, epistatic QTLs were detected in all datasets. DISCUSSION: The observed interactions demonstrated that the phenotypic effect of inheriting an allele deviated between half-sib families. Gene-by-gene interactions were also suggested, where the combined effect of two loci resulted in a genetic effect upon phenotypic variance, while no genetic effect was detected when the two loci were considered separately. To our knowledge, this is the first documentation of epistasis in a quantitative trait in Atlantic salmon. These novel results are of relevance for breeding programs, and for predicting the evolutionary consequences of domestication-introgression in wild populations.

Plasticity in growth of farmed and wild Atlantic salmon: is the increased growth rate of farmed salmon caused by evolutionary adaptations to the commercial diet?

BACKGROUND: Domestication of Atlantic salmon for commercial aquaculture has resulted in farmed salmon displaying substantially higher growth rates than wild salmon under farming conditions. In contrast, growth differences between farmed and wild salmon are much smaller when compared in the wild. The mechanisms underlying this contrast between environments remain largely unknown. It is possible that farmed salmon have adapted to the high-energy pellets developed specifically for aquaculture, contributing to inflated growth differences when fed on this diet. We studied growth and survival of 15 families of farmed, wild and F1 hybrid salmon fed three contrasting diets under hatchery conditions; a commercial salmon pellet diet, a commercial carp pellet diet, and a mixed natural diet consisting of preserved invertebrates commonly found in Norwegian rivers. RESULTS: For all groups, despite equal numbers of calories presented by all diets, overall growth reductions as high 68 and 83%, relative to the salmon diet was observed in the carp and natural diet treatments, respectively. Farmed salmon outgrew hybrid (intermediate) and wild salmon in all treatments. The relative growth difference between wild and farmed fish was highest in the carp diet (1: 2.1), intermediate in the salmon diet (1:1.9) and lowest in the natural diet (1:1.6). However, this trend was non-significant, and all groups displayed similar growth reaction norms and plasticity towards differing diets across the treatments. CONCLUSIONS: No indication of genetic-based adaptation to the form or nutritional content of commercial salmon diets was detected in the farmed salmon. Therefore, we conclude that diet alone, at least in the absence of other environmental stressors, is not the primary cause for the large contrast in growth differences between farmed and wild salmon in the hatchery and wild. Additionally, we conclude that genetically-increased appetite is likely to be the primary reason why farmed salmon display higher growth rates than wild salmon when fed ad lib rations under hatchery conditions. Our results contribute towards an understanding of the potential genetic changes that have occurred in farmed salmon in response to domestication, and the potential mechanisms underpinning genetic and ecological interactions between farmed escapees and wild salmonids.

Effect of Dose on Intra-Articular Amikacin Sulfate Concentrations Following Intravenous Regional Limb Perfusion in Horses.

OBJECTIVE: To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. STUDY DESIGN: Randomized crossover experiment. ANIMALS: Six adult horses. METHODS: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period). Amikacin concentrations were quantified in synovial fluid collected from the middle carpal and metacarpophalangeal joints at 25 minutes, and 24, 36, and 48 hours after IVRLP. Minimum inhibitory concentrations (MIC) were determined from equine bacterial isolates and ability to reach target amikacin concentrations were compared. RESULTS: Overall, middle carpal joint amikacin concentrations were higher following IVRLP with 3 g amikacin compared to 2 g (P=.031), with significant differences at 25 minutes (P=.002) and 24 hours (P=.021). No differences were observed between doses in the metacarpophalangeal joint (P=.267). Target amikacin concentrations for Staphylococcus aureus and coagulase-negative staphylococci were achieved in middle carpal and metacarpophalangeal joints at 25 minutes with both dosages and for Escherichia coli and Actinobacillus spp. in the middle carpal joint at 25 minutes with 3 g. Target concentrations were not achieved for Enterococcus spp, Pseudomonas spp, or Streptococcus equi ssp. zooepidemicus. CONCLUSION: A 3 g amikacin dose is not justified in the majority of distal limb injuries, but should be reserved for isolates with an MIC higher than that achievable with a 2 g dose. Daily IVRLP may be necessary based on our results.

Sialoendoscopy as a treatment for an obstructed mandibular salivary duct in a horse.

A 14-year-old Quarter Horse was examined for a draining tract of 8 months' duration on the right mandible that was non-responsive to antibiotic therapy and surgical therapy. Further investigation and subsequent treatment with sialoendoscopy and ultrasonography were performed to relieve an obstruction of plant awns in the mandibular salivary duct.

Sialo-endoscopie comme traitement pour un canal salivaire mandibulaire bloqué chez un cheval. Un cheval Quarter Horse âgé de 14 ans a été examiné pour une fistule purulente d'une durée de 8 mois à la mandibule droite qui ne répondait pas à la thérapie antibiotique et à la thérapie chirurgicale. De nouvelles investigations et le traitement subséquent à l'aide de la sialo-endoscopie et de l'échographie ont été réalisés pour éliminer un blocage du canal salivaire mandibulaire par des barbes de plantes.(Traduit par Isabelle Vallières).

Inflammation and acne: putting the pieces together.

Acne vulgaris is a common skin disease in which abnormal desquamation, excess sebum production, proliferation of Propionibacterium acnes, and production of proinflammatory mediators all contribute to the pathogenesis of the disease. A review of the literature shows that our current understanding of acne pathogenesis continues to evolve. Recent data suggests that inflammatory mediators may play a more important role than previously realized; however, how these mediators work independently as well as together in acne lesion progression is not well understood. Several cell types and mediators involved in the pathology of acne are responsible for producing or exacerbating an inflammatory response. Here, we present an updated theoretical model of acne lesion progression that highlights the role inflammatory mediators may play throughout acne lesion development.

Antegrade intramedullary nailing for fifth metacarpal neck fractures: a systematic review and meta-analysis.

PURPOSE: We investigated the outcomes of the antegrade intramedullary nailing (AIMN) compared to other surgical modalities in the treatment for fifth metacarpal neck fractures via a systematic review. METHODS: Pain, functional scores, grip strength, total active motion (TAM), the range of motion (ROM) of the fifth metacarpal joint, complications and patient satisfaction were set to be the primary outcomes. The data were evaluated using a modified version of the Cochrane Collaboration tool. RESULTS: We identified four studies, comprising 163 participants, which met the inclusion criteria. Meta-analyses showed that (a) AIMN demonstrated significantly better results in relation to GS at 12 months (p < 0.0001), TAM (p = 0.01) and ROM of the fifth finger (p = 0.0001); (b) AIMN technique yielded significantly lesser residual angulation at the site of fracture (p = 0.05); (c) AIMN significantly demonstrated fewer complications (p = 0.05); (d) there was a trend for better pain scores when using AIMN. CONCLUSIONS: Though the amount of evidence was derived from just four small sample-sized studies, our findings suggested that the AIMN technique could have some advantages over the use of plates or other types of pinning in the treatment for the fifth metacarpal neck fractures. We highlighted the need for a standardization of the outcomes and their corresponding units related to this specific type of fracture. Editors and reviewers should incite authors to provide the standard deviation values for the reported means. LEVEL OF EVIDENCE: Therapeutic II.

Ab Interno Canaloplasty and Trabeculotomy Outcomes for Mild, Moderate, and Advanced Open-Angle Glaucoma: A ROMEO Analysis.

Purpose: To determine if there was an association between severity of glaucoma and intraocular pressure (IOP) and medication (med) outcomes for patients in the ROMEO (Retrospective, Observational, Multicenter Evaluation of OMNI) study. Setting: Eleven ophthalmology practices in 8 US states. Design: Post-hoc analysis of all eyes enrolled and treated with ab interno canaloplasty and trabeculotomy in the retrospective, multicenter ROMEO study. Methods: Eyes were grouped according to visual field mean deviation (MD): mild (MD better than -6 dB), moderate (MD between -6 and -12 dB), advanced (-12 dB or worse). IOP and med outcomes at 12 months were compared across groups. Least squares regression was used to assess the relationship of MD with month 12 IOP. Outcomes for 1st and last MD deciles were compared as a sensitivity analysis. Results: One hundred and twenty-seven eyes were available for analysis including 79 mild, 42 moderate, 6 advanced. Most eyes had a reduction in IOP at Month 12 (70%) with most at 18 mmHg or less. Percentage IOP reduction was similar across the groups (mild 16.9%, moderate 18.6%, advanced 18.0%) with mean month 12 IOP between 14 and 16 mmHg. Medications were also reduced in all three groups; -0.8 (mild, P < 0.001), -0.55 (moderate, P < 0.05), and -1.0 (advanced, P = 0.139, ns). Regression analysis revealed no relationship between month 12 IOP and MD. Med reductions were observed for all groups with a reduction of 1 or more medications seen in (%, 95% CI) 69%, 59-79 (mild), 50%, 35-65 (moderate), and 60%, 21-99 (advanced). Secondary interventions tended to have greater incidence with worse MD likely reflecting lower desired IOP targets. Conclusion: Analysis of data from the ROMEO study suggests that similar meaningful IOP and med reductions can be expected across the range of disease severity studied.

A genetic method to infer ploidy and aberrant inheritance in triploid organisms.

Polyploidy occurs naturally across eukaryotic lineages and has been harnessed in the domestication of many crops and vertebrates. In aquaculture, triploidy can be induced as a biocontainment strategy, as it creates a reproductive barrier preventing farm-to-wild introgression, which is currently a major conservation issue for the industry. However, recent work suggests that triploidisation protocols may, on occasion, produce 'failed triploids' displaying diploidy, aneuploidy and aberrant inheritance. The potentially negative consequences for conservation and animal welfare motivate the need for methods to evaluate the success of ploidy-manipulation protocols early in the production process. We developed a semi-automated version of the MAC-PR (microsatellite DNA allele counting - peak ratios) method to resolve the allelic configuration of large numbers of individuals across a panel of microsatellite markers that can be used to infer ploidy, pedigree and inheritance aberrations. We demonstrate an application of the approach using material from a series of Atlantic salmon (Salmo salar) breeding experiments where ploidy was manipulated using a hydrostatic pressure treatment. We validated the approach to infer ploidy against blood smears, finding a > 99% agreement between these methods, and demonstrate its potential utility to infer ploidy as early as the embryonic stage. Furthermore, we present tools to assign diploid and triploid progeny to families and to detect aberrant inheritance, which may be useful for breeding programmes that utilise ploidy manipulation techniques. The approach adds to the ploidy verification toolbox. The increased precision in detecting ploidy and inheritance aberrations will facilitate the ability of triploidisation programmes to prevent farm-to-wild introgression.

Decreased systemic IGF-1 in response to calorie restriction modulates murine tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression.

Calorie restriction (CR) prevents obesity and has potent anticancer effects associated with altered hormones and cytokines. We tested the hypothesis that CR inhibits MC38 mouse colon tumor cell growth through modulation of hormone-stimulated nuclear factor (NF)-κB activation and protumorigenic gene expression. Female C57BL/6 mice were randomized (n = 30/group) to receive control diet or 30% CR diet. At 20 wk, 15 mice/group were killed for body composition analysis. At 21 wk, serum was obtained for hormone analysis. At 22 wk, mice were injected with MC38 cells; tumor growth was monitored for 24 d. Gene expression in excised tumors and MC38 cells was analyzed using real-time RT-PCR. In vitro MC38 NF-κB activation (by p65 ELISA and immunofluorescence) were measured in response to varying IGF-1 concentrations (1-400 ng/mL). Relative to controls, CR mice had decreased tumor volume, body weight, body fat, serum IGF-1, serum leptin, and serum insulin, and increased serum adiponectin (P < 0.05, each). Tumors from CR mice, versus controls, had downregulated inflammation- and/or cancer-related gene expression, including interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, cyclooxygenase-2, chemokine (C-C motif) ligand-2, S100A9, and F4/80, and upregulated 15-hydroxyprostaglandin dehydrogenase expression. In MC38 cells in vitro, IGF-1 increased NF-κB activation and NF-κB downstream gene expression (P < 0.05, each). We conclude that CR, in association with reduced systemic IGF-1, modulates MC38 tumor growth, NF-κB activation, and inflammation-related gene expression. Thus, IGF-1 and/or NF-κB inhibition may pharmacologically mimic the anticancer effects of CR to break the obesity-colon cancer link.

Identification of molecular phenotypic descriptors of breast capsular contracture formation using informatics analysis of the whole genome transcriptome.

Breast capsular contracture formation following silicone implant augmentation/reconstruction is a common complication that remains poorly understood. The aim of this study was to identify potential biomarkers implicated in breast capsular contracture formation by using, for the first time, whole genome arrays. Biopsy samples were taken from 18 patients (23 breast capsules) with Baker Grade I-II (Control) and Baker Grade III-IV (Contracted). Whole genome microarrays were performed and six significantly dysregulated genes were selected for further validation with quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Hematoxylin and eosin was also carried out to compare the histological characteristics of control and contracted samples. Microarray results showed that aggrecan, tissue inhibitor of metalloproteinase 4 (TIMP4), and tumor necrosis factor superfamily (ligand) member 11 were significantly down-regulated in contracted capsules; while matrix metallopeptidase 12, serum amyloid A 1, and interleukin 8 (IL8) were significantly up-regulated. The dysregulation of aggrecan, tumor necrosis factor superfamily (ligand) member 11, TIMP4, and IL8 was validated by quantitative reverse transcriptase polymerase chain reaction (p < 0.05). Immunohistochemistry confirmed an increased protein expression for IL8 and matrix metallopeptidase 12 in contracted capsules (p < 0.05), and decreased protein expression of TIMP4 (p < 0.05). This study has shown, for the first time, a number of unique biomarkers of significance in capsular contracture formation. IL8 and TIMP4 may serve as potential key diagnostic, therapeutic, and prognostic biomarkers in capsular contracture formation.

Using normalisation process theory for intervention development, implementation and refinement in musculoskeletal and orthopaedic interventions: a qualitative systematic review.

BACKGROUND: Normalisation process theory (NPT) provides researchers with a set of tools to support the understanding of the implementation, normalisation and sustainment of an intervention in practice. Previous reviews of published research have explored NPT's use in the implementation processes of healthcare interventions. However, its utility in intervention research, specifically in orthopaedic and musculoskeletal interventions, remains unclear. The aim of this review is to explore how NPT (including extended NPT, ENPT) has been used in orthopaedic/musculoskeletal intervention research. METHODS: A qualitative systematic review was conducted. Two bibliographic databases (Scopus and Web of Science) and a search engine (Google Scholar) were searched for peer-reviewed journal articles citing key papers outlining the development of NPT, related methods, tools or the web-based toolkit. We included studies of any method, including protocols, and did not exclude based on published language. A data extraction tool was developed, and data were analysed using a framework approach. RESULTS: Citation searches, of the 12 key studies, revealed 10,420 citations. Following duplicate removal, title, abstract and full-text screening, 14 papers from 12 studies were included. There were 8 key findings assessed against GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research). Five were of high confidence supporting NPT/ENPT's use in the implementation process for interventions targeting a range of MSK/orthopaedic conditions. NPT/ENPT offers a useful analytical lens to focus attention and consider implementation factors robustly. There is limited evidence for the selection of NPT/ENPT and for the use of the Normalisation Measure Development instrument. Three findings of moderate confidence suggest that coherence is seen as a fundamental initial step in implementation, there is limited evidence that study population limits NPT's utility and the application of ENPT may pose a challenge to researchers. CONCLUSION: This review demonstrates NPT's utility in supporting intervention implementation for orthopaedic and musculoskeletal conditions. We have theorised the benefits ENPT offers to intervention development and refinement and recommend future researchers consider its use. We also encourage future researchers to offer clear justification for NPT's use in their methodology. TRIAL REGISTRATION: The review protocol is registered with PROSPERO (CRD42022358558).

DNA and scale reading to identify repeat spawning in Atlantic salmon: Unique insights into patterns of iteroparity.

Iteroparity represents an important but often overlooked component of life history in anadromous Atlantic salmon. Here, we combined individual DNA profiling and scale reading to identify repeat spawners among ~8000 adult salmon captured in a fish trap in the river Etne, Norway, in the period 2015-2019. Additionally, 171 outward migrating kelts were captured in the spring of 2018-2020 and identified using molecular methods to estimate weight loss since ascending the river to spawn. The overall frequency of repeat spawners identified using molecular methods and scale reading combined was 7% in females and 3% in males (5% in total). Most of these (83%) spent one full year reconditioning at sea before returning for their second spawning, with a larger body size compared with their size at first spawning, gaining on average 15.9 cm. A single female migrating back into the river for a fifth breeding season was also identified. On average, kelts lost 40% bodyweight in the river, and more female than male kelts were captured during outward migration. The date of arrival in the upstream fish trap was significantly but moderately correlated between maiden and second entry to the river for alternate and consecutive spawners. The estimated contribution from repeat spawners to the total number of eggs deposited in the river each year varied between 2% and 17% (average 12%). Molecular-based methods marginally underestimated the number of repeat spawners compared with scale reading (5% vs 7%) likely due to a small number of returning spawners not being trapped and sampled. Differences between the methods were most evident when classifying the spawning strategy (alternate or consecutive-year repeat spawners), where the scale method identified proportionally more consecutive-year repeat spawners than the molecular method. This unique data set reveals previously unstudied components of this life history strategy and demonstrates the importance of repeat spawners in population recruitment.

Minimally Invasive Glaucoma Surgery: Latest Developments and Future Challenges.

The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.

Time series covering up to four decades reveals major changes and drivers of marine growth and proportion of repeat spawners in an Atlantic salmon population.

Wild Atlantic salmon populations have declined in many regions and are affected by diverse natural and anthropogenic factors. To facilitate management guidelines, precise knowledge of mechanisms driving population changes in demographics and life history traits is needed.Our analyses were conducted on (a) age and growth data from scales of salmon caught by angling in the river Etneelva, Norway, covering smolt year classes from 1980 to 2018, (b) extensive sampling of the whole spawning run in the fish trap from 2013 onwards, and (c) time series of sea surface temperature, zooplankton biomass, and salmon lice infestation intensity.Marine growth during the first year at sea displayed a distinct stepwise decline across the four decades. Simultaneously, the population shifted from predominantly 1SW to 2SW salmon, and the proportion of repeat spawners increased from 3 to 7%. The latter observation is most evident in females and likely due to decreased marine exploitation. Female repeat spawners tended to be less catchable than males by anglers.Depending on the time period analyzed, marine growth rate during the first year at sea was both positively and negatively associated with sea surface temperature. Zooplankton biomass was positively associated with growth, while salmon lice infestation intensity was negatively associated with growth.Collectively, these results are likely to be linked with both changes in oceanic conditions and harvest regimes. Our conflicting results regarding the influence of sea surface temperature on marine growth are likely to be caused by long-term increases in temperature, which may have triggered (or coincided with) ecosystem shifts creating generally poorer growth conditions over time, but within shorter datasets warmer years gave generally higher growth. We encourage management authorities to expand the use of permanently monitored reference rivers with complete trapping facilities, like the river Etneelva, generating valuable long-term data for future analyses.

Energy balance modulates colon tumor growth: Interactive roles of insulin and estrogen.

Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colon tumor growth. Female C57BL/6 mice (6 wk) were either ovariectomized (OVX) or ovaries left intact (nonovariectomized, NOVX) and randomized to receive a (1) control, (2) 30% calorie-restricted (CR), or (3) diet-induced obese (DIO) diet regimen for 20 wk to induce differing levels of adiposity. Serum was collected and inflammatory and metabolic markers were measured using an antibody array (62 proteins) and ELISAs. Mice were subcutaneously injected with syngeneic MC38 colon cancer cells after 20 wk and sacrificed 4 wk later. CR mice had the smallest tumors irrespective of hormone status, whereas the largest tumors were observed in DIO-OVX mice. Glucose tolerance was impaired in OVX mice, being most severe in the DIO-OVX group. Cytokine arrays suggested that in CR animals, inhibition of tumor growth paralleled insulin sensitivity and associated changes in leptin, adiponectin, and IGF-BPs. Conversely, in DIO-OVX animals, tumor growth was associated with insulin and leptin resistance as well as higher levels of pro-inflammatory proteins. In vitro, leptin and adiponectin had no effect, whereas insulin induced MC38 cell proliferation and MAPK activation. Co-treatment with estrogen blocked the stimulatory effects of insulin. Thus, our in vitro and in vivo data indicate female reproductive hormones have a modulating effect on obesity-induced insulin resistance and inflammation, which may directly or indirectly influence CRC progression.

Domestication-induced reduction in eye size revealed in multiple common garden experiments: The case of Atlantic salmon (Salmo salar L.).

Domestication leads to changes in traits that are under directional selection in breeding programmes, though unintentional changes in nonproduction traits can also arise. In offspring of escaping fish and any hybrid progeny, such unintentionally altered traits may reduce fitness in the wild. Atlantic salmon breeding programmes were established in the early 1970s, resulting in genetic changes in multiple traits. However, the impact of domestication on eye size has not been studied. We measured body size corrected eye size in 4000 salmon from six common garden experiments conducted under artificial and natural conditions, in freshwater and saltwater environments, in two countries. Within these common gardens, offspring of domesticated and wild parents were crossed to produce 11 strains, with varying genetic backgrounds (wild, domesticated, F1 hybrids, F2 hybrids and backcrosses). Size-adjusted eye size was influenced by both genetic and environmental factors. Domesticated fish reared under artificial conditions had smaller adjusted eye size when compared to wild fish reared under identical conditions, in both the freshwater and marine environments, and in both Irish and Norwegian experiments. However, in parr that had been introduced into a river environment shortly after hatching and sampled at the end of their first summer, differences in adjusted eye size observed among genetic groups were of a reduced magnitude and were nonsignificant in 2-year-old sea migrating smolts sampled in the river immediately prior to sea entry. Collectively, our findings could suggest that where natural selection is present, individuals with reduced eye size are maladapted and consequently have reduced fitness, building on our understanding of the mechanisms that underlie a well-documented reduction in the fitness of the progeny of domesticated salmon, including hybrid progeny, in the wild.

Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research.

Calorie restriction (CR) is arguably the most potent, broadly acting dietary regimen for suppressing the carcinogenesis process, and many of the key studies in this field have been published in Carcinogenesis. Translation of the knowledge gained from CR research in animal models to cancer prevention strategies in humans is urgently needed given the worldwide obesity epidemic and the established link between obesity and increased risk of many cancers. This review synthesizes the evidence on key biological mechanisms underlying many of the beneficial effects of CR, with particular emphasis on the impact of CR on growth factor signaling pathways and inflammatory processes and on the emerging development of pharmacological mimetics of CR. These approaches will facilitate the translation of CR research into effective strategies for cancer prevention in humans.

Genetic risks and healthy choices: creating citizen-consumers of genetic services through empowerment and facilitation.

Genetic testing to identify susceptibility to a variety of common complex diseases is increasingly becoming available. In this article, focusing on the development of genetic susceptibility testing for diet-related disease, I examine the emergence of direct-to-the-consumer genetic testing services and the (re)configuration of healthcare provision, both within and outside the specialist genetics service, in the UK. I identify two key techniques within these practices: empowerment and facilitation. Using Foucauldian social theory, I show that empowerment and facilitation are being positioned as tools for the creation of citizen-consumers who will make appropriate dietary choices, based on the results of their genetic analysis. Through these techniques, individuals are transformed into properly entrepreneurial citizens who will, through judicious choices, act to maximise their 'vital capital' (their health) and the capital of the social body. I argue that the user of these services is not purely an economic figure, making rational choices as a consumer, but that her configuration as a citizen-consumer who avails herself of genetic information and services in a proper manner ensures that she is fit to contribute to the economic life of our present.