Adapting to Regional Enforcement: Fishing Down the Governance Index

Background: Illegal, Unreported and Unregulated (IUU) fishing is a problem for marine resource managers, leading to depletion of fish stocks and negative impacts on marine ecosystems. These problems are particularly evident in regions with weak governance. Countries responsible for sustainable natural resource management in the Southern Ocean have actively worked to reduce IUU fishing in the region over a period of 15 years, leading to a sequence of three distinct peaks of IUU fishing. Methodology/Principal Findings: We reviewed existing public records relating to IUU fishing in the Southern Ocean between 1995–2009 and related this information to the governance capacity of flag states responsible for IUU vessels. IUU operators used a number of methods to adapt to enforcement actions, resulting in reduced risks of detection, apprehension and sanctioning. They changed fishing locations, vessel names and flag states, and ports for offloading IUU catches. There was a significant decrease in the proportion of IUU vessels flagged to CCAMLR countries, and a significant decrease in the average governance index of flag states. Despite a decreasing trend of IUU fishing, further actions are hampered by the regional scope of CCAMLR and the governance capacity of responsible states. Conclusions/Significance: This is the first study of long-term change in the modus operandi of IUU fishing operators, illustrating that IUU operators can adapt to enforcement actions and that such dynamics may lead to new problems elsewhere, where countries have a limited capacity. This outsourcing of problems may have similarities to natural resourc

Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics

Adverse reactions or lack of response to medications are important concerns for drug development programs. However, faithful predictions of drug metabolism and toxicity are difficult because animal models show only limited translatability to humans. Furthermore, current in vitro systems, such as hepatic cell lines or primary human hepatocyte (PHH) 2-dimensional (2D) monolayer cultures, can be used only for acute toxicity tests because of their immature phenotypes and inherent instability. Therefore, the migration to novel phenotypically stable models is of prime importance for the pharmaceutical industry. Novel 3-dimensional (3D) culture systems have been shown to accurately mimic in vivo hepatic phenotypes on transcriptomic and proteomic level, but information about their metabolic stability is lacking. Using a combination of targeted and untargeted high-resolution mass spectrometry, we found that PHHs in 3D spheroid cultures remained metabolically stable for multiple weeks, whereas metabolic patterns of PHHs from the same donors cultured as conventional 2D monolayers rapidly deteriorated. Furthermore, pharmacokinetic differences between donors were maintained in 3D spheroid cultures, enabling studies of interindividual variability in drug metabolism and toxicity. We conclude that the 3D spheroid system is metabolically stable and constitutes a suitable model for in vitro studies of long-term drug metabolism and pharmacokinetics.Peer reviewe

Importance of organic farming research in Sweden for innovations and increased sustainability in agriculture

Organic farming is known to be a knowledge intensive production system and there is a strong need for new knowledge and innovations to achieve increased sustainability. Furthermore, many of the research goals defined in national and international research strategies for organic agriculture are addressing questions relating to the development of more sustainable food and farming systems in general. Organic systems can thus be seen as a fore-runner and an innovation system to sustainable food and farming (TP Organics, 2009; EPOK, 2013)

Changing musical emotion: A computational rule system for modifying score and performance

CMERS system architecture has been implemented in the programming language scheme, and it uses the improvised music programming environment with the objective to provide researchers with a tool for testing the relationships between musical features and emotion. A music work represented in CMERS uses the music object hierarchy that is based on GTTM's grouping structure and is automatically generated from the phrase boundary markup and MIDI file. The Mode rule type of CMERS converts a note into those of the parallel mode and no change in pitch height occurs when converting to the parallel mode. It is reported that the odds of correctness with CMERS are approximately five times greater than that of DM. The repeated-measures analysis of variance for valence shows a significant difference between systems with F (1, 17) = 45.49, p < .0005 and the interaction between system and quadrant is significant with F (3, 51) = 4.23, p = .01, which indicates that CMERS is extensively more effective at correctly influencing valence than DM. c 2010 Massachusetts Institute of Technology

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

Reproducibility of $\textit{in vivo}$ research using the mouse as a model organism depends on many factors, including experimental design, strain or stock, experimental protocols, and methods of data evaluation. Gross and histopathology are often the endpoints of such research and there is increasing concern about the accuracy and reproducibility of diagnoses in the literature. To reproduce histopathological results, the pathology protocol, including necropsy methods and slide preparation, should be followed by interpretation of the slides by a pathologist familiar with reading mouse slides and familiar with the consensus medical nomenclature used in mouse pathology. Likewise, it is important that pathologists are consulted as reviewers of manuscripts where histopathology is a key part of the investigation. The absence of pathology expertise in planning, executing and reviewing $\textit{in vivo}$ research using mice leads to questionable pathology-based findings and conclusions from studies, even in high-impact journals. We discuss the various aspects of this problem, give some examples from the literature and suggest solutions.This work was supported in part by US National Institutes of Health grants R01 AR049288, CA089713 and R21 AR063781 (to J.P.S.) and by The Warden and Fellows of Robinson College, Cambridge (to P.N.S.)

Cardiac fibrosis in aging mice

Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. In previous mouse breeding studies between these DCC susceptible and the DCC-resistant strain C57BL/6J, 4 genetic loci harboring genes involved in DCC inheritance were identified and subsequently termed Dyscalc loci 1 through 4. Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. Using genotype and phenotype information of the 28 investigated strains, we performed genome-wide association studies (GWAS) and identified the most significant associations on chromosome (Chr) 15 at 72 million base pairs (Mb) (P < 10(-13)) and Chr 4 at 122 Mb (P < 10(-11)) and 134 Mb (P < 10(-7)). At the Chr 15 locus, Col22a1 and Kcnk9 were identified. Both have been reported to be morphologically and functionally important in the heart muscle. The strongest Chr 4 associations were located approximately 6 Mb away from the Dyscalc 2 quantitative trait locus peak within the boundaries of the Extl1 gene and in close proximity to the Trim63 and Cap1 genes. In addition, a single-nucleotide polymorphism association was found on chromosome 11. This study provides evidence for more than the previously reported 4 genetic loci determining cardiac fibrosis and DCC. The study also highlights the power of GWAS in the mouse for dissecting complex genetic traits.The authors thank Jesse Hammer and Josiah Raddar for technical assistance. Research reported in this publication was supported by the Ellison Medical Foundation, Parker B. Francis Foundation, and the National Institutes of Health (R01AR055225 and K01AR064766). Mouse colonies were supported by the National Institutes of Health under Award Number AG025707 for the Jackson Aging Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Jackson Laboratory Shared Scientific Services were supported in part by a Basic Cancer Center Core Grant from the National Cancer Institute (CA34196).This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00335-016-9634-

Maternal exposure to UV filters:Associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes

Background: Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern. Objectives: To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. Methods: Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. Results: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. Conclusions: Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children’s health

A new method to explore the spectral impact of the piriform fossae on the singing voice : Benchmarking using MRI-based 3D-printed vocal tracts

The piriform fossae are the 2 pear-shaped cavities lateral to the laryngeal vestibule at the lower end of the vocal tract. They act acoustically as side-branches to the main tract, resulting in a spectral zero in the output of the human voice. This study investigates their spectral role by comparing numerical and experimental results of MRI-based 3D printed Vocal Tracts, for which a new experimental method (based on room acoustics) is introduced. The findings support results in the literature: the piriform fossae create a spectral trough in the region 4–5 kHz and act as formants repellents. Moreover, this study extends those results by demonstrating numerically and perceptually the impact of having large piriform fossae on the sung output

CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients

BACKGROUND: CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival. METHODS: A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports. RESULTS: Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C8*4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9*3/*1*/*2/*1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11-5.79). The effect appeared to be driven by CYP2C8*3, adjusted HR 8.56 (95%CI 1.53-51.1). CONCLUSION: Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients