Essential nucleotide- and protein-dependent functions of Actb/β-actin

The highly similar cytoplasmic β- and γ-actins differ by only four functionally similar amino acids, yet previous in vitro and in vivo data suggest that they support unique functions due to striking phenotypic differences between Actb and Actg1 null mouse and cell models. To determine whether the four amino acid variances were responsible for the functional differences between cytoplasmic actins, we gene edited the endogenous mouse Actb locus to translate γ-actin protein. The resulting mice and primary embryonic fibroblasts completely lacked β-actin protein, but were viable and did not present with the most overt and severe cell and organismal phenotypes observed with gene knockout. Nonetheless, the edited mice exhibited progressive high-frequency hearing loss and degeneration of actin-based stereocilia as previously reported for hair cell-specific Actb knockout mice. Thus, β-actin protein is not required for general cellular functions, but is necessary to maintain auditory stereocilia

Recruitment Variability in North Atlantic Cod and Match-Mismatch Dynamics

Background Fisheries exploitation, habitat destruction, and climate are important drivers of variability in recruitment success. Understanding variability in recruitment can reveal mechanisms behind widespread decline in the abundance of key species in marine and terrestrial ecosystems. For fish populations, the match-mismatch theory hypothesizes that successful recruitment is a function of the timing and duration of larval fish abundance and prey availability. However, the underlying mechanisms of match-mismatch dynamics and the factors driving spatial differences between high and low recruitment remain poorly understood. Methodology/Principal Findings We used empirical observations of larval fish abundance, a mechanistic individual-based model, and a reanalysis of ocean temperature data from 1960 to 2002 to estimate the survival of larval cod (Gadus morhua). From the model, we quantified how survival rates changed during the warmest and coldest years at four important cod spawning sites in the North Atlantic. The modeled difference in survival probability was not large for any given month between cold or warm years. However, the cumulative effect of higher growth rates and survival through the entire spawning season in warm years was substantial with 308%, 385%, 154%, and 175% increases in survival for Georges Bank, Iceland, North Sea, and Lofoten cod stocks, respectively. We also found that the importance of match-mismatch dynamics generally increased with latitude. Conclusions/Significance Our analyses indicate that a key factor for enhancing survival is the duration of the overlap between larval and prey abundance and not the actual timing of the peak abundance. During warm years, the duration of the overlap between larval fish and their prey is prolonged due to an early onset of the spring bloom. This prolonged season enhances cumulative growth and survival, leading to a greater number of large individuals with enhanced potential for survival to recruitment

Structure and functioning of four North Atlantic ecosystems - A comparative study

The epi- and mesopelagic ecosystems of four sub-polar ocean basins, the Labrador, Irminger, Iceland and Norwegian seas, were surveyed during two legs from Bergen, Norway, to Nuuk, Greenland, and back to Bergen. The survey was conducted from 1 May to 14 June, and major results were published in five papers (Drinkwater et al., Naustvoll et al., Strand et al., Melle et al., this issue, and Klevjer et al., this issue a, this issue b). In the present paper, the structures of the ecosystem are reviewed, and aspects of the functioning of the ecosystems examined, focusing on a comparison of trophic relationships in the four basins. In many ways, the ecosystems are similar, which is not surprising since they are located at similar latitudes and share many hydrographic characteristics, like input of both warm and saline Atlantic water, as well as cold and less saline Arctic water. Literature review suggests that total annual primary production is intermediate in the eastern basins and peaks in the Labrador Sea, while the Irminger Sea is the most oligotrophic sea. This was not reflected in the measurements of different trophic levels taken during the cruise. The potential new production was estimated to be higher in the Irminger Sea than in the eastern basins, and while the biomass of mesozooplankton was similar across basins, the biomass of mesopelagic micronekton was about one order of magnitude higher in the western basins, and peaked in the Irminger Sea, where literature suggests annual primary production is at its lowest. The eastern basins hold huge stocks of pelagic planktivore fish stocks like herring, mackerel and blue whiting, none of which are abundant in the western seas. As both epipelagic nekton and mesopelagic micronekton primarily feed on the mesozooplankton, there is likely competitive interactions between the epipelagic and mesopelagic, but we're currently unable to explain the estimated ~1 order of magnitude difference in micronekton standing stock. The results obtained during the survey highlight that even if some aspects of pelagic ecosystems are well understood, we currently do not understand overall pelagic energy flow in the North Atlantic.publishedVersio

Self reported skin morbidity and ethnicity: a population-based study in a Western community

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown ethnic differences concerning cardio-vascular disease, diabetes and mental health. Little is known about ethnic differences in skin morbidity. The purpose of this study was to describe possible ethnic differences in self-reported skin morbidity in a Western urban community.</p> <p>Methods</p> <p>The design was cross sectional. 40 888 adults in Oslo, Norway, received a postal questionnaire providing information on socio-demographic factors and self-reported health, including items on skin complaints.</p> <p>Results</p> <p>18770 individuals answered the questionnaire. In the sample 84% were from Norway. The largest immigrant group was from Western countries (5%) and the Indian Subcontinent (3%). Itch was the most prevalent reported skin symptom (7%), and was significantly more reported by men from East Asia (18%) and Middle East/North Africa (13%). The same observations were seen for reported dry and sore skin. Hair loss was a dominating complaint for men from the Indian Subcontinent and the Middle East/North Africa (23% and 25%) and for women from the same ethnic groups. Women from Sub-Saharan Africa reported significantly more pimples than in the other groups (17%).</p> <p>Conclusion</p> <p>The study showed that there were significant differences in self-reported skin complaints among ethnic groups. Issues concerning the cultural value of some skin symptoms should be examined further.</p

Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study

BACKGROUND: The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors. METHODS AND FINDINGS: This multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass whole genome sequencing (ULP-WGS) of plasma cell-free DNA (cfDNA) to distinguish between MPNST and PN in patients with NF1. Following in silico enrichment for short cfDNA fragments and copy number analysis to estimate the fraction of plasma cfDNA originating from tumor (tumor fraction), we developed a noninvasive classifier that differentiates MPNST from PN with 86% pretreatment accuracy (91% specificity, 75% sensitivity) and 89% accuracy on serial analysis (91% specificity, 83% sensitivity). Healthy controls without NF1 (participants = 16, plasma samples = 16), PN (participants = 23, plasma samples = 23), and MPNST (participants = 14, plasma samples = 46) cohorts showed significant differences in tumor fraction in plasma (P = 0.001) as well as cfDNA fragment length (P \u3c 0.001) with MPNST samples harboring shorter fragments and being enriched for tumor-derived cfDNA relative to PN and healthy controls. No other covariates were significant on multivariate logistic regression. Mutational analysis demonstrated focal NF1 copy number loss in PN and MPNST patient plasma but not in healthy controls. Greater genomic instability including alterations associated with malignant transformation (focal copy number gains in chromosome arms 1q, 7p, 8q, 9q, and 17q; focal copy number losses in SUZ12, SMARCA2, CDKN2A/B, and chromosome arms 6p and 9p) was more prominently observed in MPNST plasma. Furthermore, the sum of longest tumor diameters (SLD) visualized by cross-sectional imaging correlated significantly with paired tumor fractions in plasma from MPNST patients (r = 0.39, P = 0.024). On serial analysis, tumor fraction levels in plasma dynamically correlated with treatment response to therapy and minimal residual disease (MRD) detection before relapse. Study limitations include a modest MPNST sample size despite accrual from 2 major referral centers for this rare malignancy, and lack of uniform treatment and imaging protocols representing a real-world cohort. CONCLUSIONS: Tumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations

The Scandinavian Sarcoma Group Central Register : 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.Peer reviewe

IMBeR into the future Science Plan and Implementation Strategy 2016-2025

The Integrated Marine Biosphere Research (IMBeR) project, formerly the Integrated Marine Biogeochemistry and Ecosystem Research (IMBER1) project, is a global environmental change research initiative. Since its start in 2005, IMBeR has advanced understanding about potential marine environmental effects of global change, and the impacts and linkages to human systems at multiple scales. It is apparent that complex environmental issues and associated societal/sustainability choices operate at and across the interfaces of natural and social sciences and the humanities, and require both basic, curiosity-driven research and problem-driven, policy-relevant research. Collaborative, disciplinary, interdisciplinary, transdisciplinary and integrated research that addresses key ocean science issues generated by and/or impacting society is required to provide evidence-based knowledge and guidance, along with options for policy-makers, managers and marine-related communities, to help achieve sustainability of the marine realm under global change. This recognition underlies a new vision, “Ocean sustainability under global change for the benefit of society”, to guide IMBeR research for the next decade (2016-2025). This vision recognises that the evolution of marine ecosystems (including biogeochemical cycles and human systems) is linked to natural and anthropogenic drivers and stressors, as articulated in the new IMBeR research goal to, “Understand, quantify and compare historic and present structure and functioning of linked ocean and human systems to predict and project changes including developing scenarios and options for securing or transitioning towards ocean sustainability”. To implement its new vision and goal in the next decade, IMBeR’s mission is to, “Promote integrated marine research and enable capabilities for developing and implementing ocean sustainability options within and across the natural and social sciences, and communicate relevant information and knowledge needed by society to secure sustainable, productive and healthy oceans”. This Science Plan and Implementation Strategy provides a 10-year (2016-2025) marine research agenda for IMBeR. It is developed around three Grand Challenges (GC, see Graphical Executive Summary) focusing on climate variability, global change and drivers and stressors. The qualitative and quantitative understanding of historic and present ocean variability and change (Grand Challenge I) are the basis for scenarios, projections and predictions of the future (Grand Challenge II). These are linked in Grand Challenge III to understand how humans are causing the variability and changes, and how they, in turn, are impacted by these changes, including feedbacks between the human and ocean systems. Priority research areas with overarching and specific research questions are identified for each Grand Challenge. The Grand Challenges are supplemented with Innovation Challenges (IC, see graphical executive summary) that focus on new topics for IMBeR where research is needed and where it is believed that major achievements can be made within three to five years. The Innovation Challenges also provide a means for IMBeR to adjust its focus as major science discoveries are made and new priorities arise, especially regarding scientific innovations

Striving to promote male involvement in maternal health care in rural and urban settings in Malawi - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Understanding the strategies that health care providers employ in order to invite men to participate in maternal health care is very vital especially in today's dynamic cultural environment. Effective utilization of such strategies is dependent on uncovering the salient issues that facilitate male participation in maternal health care. This paper examines and describes the strategies that were used by different health care facilities to invite husbands to participate in maternal health care in rural and urban settings of southern Malawi.</p> <p>Methods</p> <p>The data was collected through in-depth interviews from sixteen of the twenty health care providers from five different health facilities in rural and urban settings of Malawi. The health facilities comprised two health centres, one district hospital, one mission hospital, one private hospital and one central hospital. A semi-structured interview guide was used to collect data from health care providers with the aim of understanding strategies they used to invite men to participate in maternal health care.</p> <p>Results</p> <p>Four main strategies were used to invite men to participate in maternal health care. The strategies were; health care provider initiative, partner notification, couple initiative and community mobilization. The health care provider initiative and partner notification were at health facility level, while the couple initiative was at family level and community mobilization was at village (community) level. The community mobilization had three sub-themes namely; male peer initiative, use of incentives and community sensitization. The sustainability of each strategy to significantly influence behaviour change for male participation in maternal health care is discussed.</p> <p>Conclusion</p> <p>Strategies to invite men to participate in maternal health care were at health facility, family and community levels. The couple strategy was most appropriate but was mostly used by educated and city residents. The male peer strategy was effective and sustainable at community level. There is need for creation of awareness in men so that they sustain their participation in maternal health care activities of their female partners even in the absence of incentives, coercion or invitation.</p