Influence of Blood Contamination on Bond Strength of a Self-Etching System

OBJECTIVES: To detect the influence of blood contamination (BC) on the bond strength (BS) of a self-etching bonding system (SES) to enamel and dentine. METHODS: 25 human molars were longitudinally sectioned on the mesio-distal axis in order to obtain 50 specimens, which were embedded in acrylic resin. At first, the specimens were ground to expose a flat surface of enamel, and a bond strength test was performed. Afterwards, the samples were ground again in order to obtain a flat surface of dentine. Ten groups (total: n=100) were assigned according to substrate (enamel and dentine), step in the bonding sequence when contamination occurred (before the acidic primer and after the bonding resin), and contamination treatment (dry or rinse and dry procedure). Fresh human blood was introduced either before or after SES application (Clearfil SE Bond) and treated with air drying, or by rinsing and drying following application. Composite resin (Filtek Z-250,3M ESPE) was applied as inverted, truncated cured cones that were debonded in tension. RESULTS: The mean tensile BS values (MPa) for enamel/dentine were 19.4/23.0 and 17.1/10.0 for rinse-and-dry treatment (contamination before and after SES, respectively); while the measurements for the dry treatment, 16.2/23.3 and 0.0/0.0 contamination before and after SES, respectively. CONCLUSIONS: It was determined that blood contamination impaired adhesion to enamel and dentine when it occurred after bond light curing. Among the tested contamination treatments, the rinse-and-dry treatment produced the highest bond strength with BC after SES application, but it was not sufficient to recover the BS in the contamination-free group

Meltwater layer dynamics in a central Arctic lead: Effects of lead width, re-freezing, and mixing during late summer

17 pages, 9 figures, 1 table.-- Data accessibility statement: The data analyzed in this study were mainly retrieved from links below: RINKO profiler-derived variables: https://doi.pangaea.de/10.1594/PANGAEA.945337, water sampling derived variables: https://doi.pangaea.de/10.1594/PANGAEA.945285, meteorological variables: https://doi.org/10.1594/PANGAEA.935267, and MSS profiler-derived variables: https://doi.org/10.1594/PANGAEA.939816. The oxygen isotope data stems from the ISOLAB Facility at AWI in PotsdamLeads play an important role in the exchange of heat, gases, vapour, and particles between seawater and the atmosphere in ice-covered polar oceans. In summer, these processes can be modified significantly by the formation of a meltwater layer at the surface, yet we know little about the dynamics of meltwater layer formation and persistence. During the drift campaign of the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC), we examined how variation in lead width, re-freezing, and mixing events affected the vertical structure of lead waters during late summer in the central Arctic. At the beginning of the 4-week survey period, a meltwater layer occupied the surface 0.8 m of the lead, and temperature and salinity showed strong vertical gradients. Stable oxygen isotopes indicate that the meltwater consisted mainly of sea ice meltwater rather than snow meltwater. During the first half of the survey period (before freezing), the meltwater layer thickness decreased rapidly as lead width increased and stretched the layer horizontally. During the latter half of the survey period (after freezing of the lead surface), stratification weakened and the meltwater layer became thinner before disappearing completely due to surface ice formation and mixing processes. Removal of meltwater during surface ice formation explained about 43% of the reduction in thickness of the meltwater layer. The remaining approximate 57% could be explained by mixing within the water column initiated by disturbance of the lower boundary of the meltwater layer through wind-induced ice floe drift. These results indicate that rapid, dynamic changes to lead water structure can have potentially significant effects on the exchange of physical and biogeochemical components throughout the atmosphere–lead–underlying seawater systemThis study was supported by the Japan Society for the Promotion of Science (grant numbers: JP18H03745; JP18KK0292; JP17KK0083; JP17H04715; JP20H04345) and by a grant from the Joint Research Program of the Japan Arctic Research NetworkCenter. MM and HM are supported through the German Federal Ministry of Education and Research (grant number 03FO869A). ALW and KS were funded through the UK Natural Environment Research Council (NERC) (Grants No NE/S002596/1 and NE/S002502/1, respectively). ESD was supported by NERC through the EnvEast Doctoral Training Partnership (NE/L002582/1), as well as NERC and the Department for Business, Energy & Industrial Strategy (BEIS) through the UK Arctic Office. EJC was supported by the National Science Foundation (USA) NSF OPP 1821911 and NSF Graduate Research Fellowship. CG was funded through the Spanish funding Agency (AEI) though the grant PCI 2019-111844-2. MMS was funded through NSF OPP-1724467, OPP-1724748, and OPP-2138787. DB was funded through the German funding Agency (DFG) through grant BA1689/4-1With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Absence of Ataxin-3 Leads to Enhanced Stress Response in C. elegans

Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never been described

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Overview of the MOSAiC expedition: Physical oceanography

Arctic Ocean properties and processes are highly relevant to the regional and global coupled climate system, yet still scarcely observed, especially in winter. Team OCEAN conducted a full year of physical oceanography observations as part of the Multidisciplinary drifting Observatory for the Study of the Arctic Climate (MOSAiC), a drift with the Arctic sea ice from October 2019 to September 2020. An international team designed and implemented the program to characterize the Arctic Ocean system in unprecedented detail, from the seafloor to the air-sea ice-ocean interface, from sub-mesoscales to pan-Arctic. The oceanographic measurements were coordinated with the other teams to explore the ocean physics and linkages to the climate and ecosystem. This paper introduces the major components of the physical oceanography program and complements the other team overviews of the MOSAiC observational program. Team OCEAN’s sampling strategy was designed around hydrographic ship-, ice- and autonomous platform-based measurements to improve the understanding of regional circulation and mixing processes. Measurements were carried out both routinely, with a regular schedule, and in response to storms or opening leads. Here we present alongdrift time series of hydrographic properties, allowing insights into the seasonal and regional evolution of the water column from winter in the Laptev Sea to early summer in Fram Strait: freshening of the surface, deepening of the mixed layer, increase in temperature and salinity of the Atlantic Water. We also highlight the presence of Canada Basin deep water intrusions and a surface meltwater layer in leads. MOSAiC most likely was the most comprehensive program ever conducted over the ice-covered Arctic Ocean. While data analysis and interpretation are ongoing, the acquired datasets will support a wide range of physical oceanography and multi-disciplinary research. They will provide a significant foundation for assessing and advancing modeling capabilities in the Arctic Ocean

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Profiles of temperature, salinity and dissolved oxygen measured by a handheld CTD in a lead during expedition PS122/5 (MOSAiC Leg 5) to the central Arctic in August-September 2020

18 profiles of seawater temperature, salinity and dissolved oxygen were obtained in a lead next to the MOSAiC Leg5 ice camp between 23 August and 17 September 2020. A Rinko handheld CTD (JFE Advantech Co., Ltd., Japan) was carefully lowered into the lead on a regular basis to determine the spatial distribution and temporal evolution of the stratification in the upper 5 m. The several meter wide lead had formed from an initially small crack through the main ice floe on 24 August 2020. Ice dynamics caused the lead to successively open and close throughout the study period. Lead widths were recorded via a laser distance meter during each profile. A fresh meltwater layer was detected at several locations beneath the floe, and was also observed in the lead. As part of a dedicated study, the present dataset documents the evolution of this layer