167 research outputs found
Tracking construction material over space and time: Prospective and geo-referenced modeling of building stocks and construction material flows
Construction material plays an increasingly important role in the environmental impacts of buildings. In order to investigate impacts of materials on a building level, we present a bottom-up building stock model that uses three dimensional and geo-referenced building data to determine volumetric information of material stocks in Swiss residential buildings. We used a probabilistic modeling approach to calculate future material flows for the individual buildings. We investigated six scenarios with different assumptions concerning per capita floor area, building stock turnover, and construction material. The Swiss building stock will undergo important structural changes by 2035. While this will lead to a reduced number in new constructions, material flows will increase. Total material inflow decreases by almost half while outflows double. In 2055 the total amount of material in- and outflows are almost equal, which represents an important opportunity to close construction material cycles. Total environmental impacts due to production and disposal of construction material remain relatively stable over time. The cumulated impact is slightly reduced for the wood-based scenario. The scenario with more insulation material leads to slightly higher material-related emissions. An increase per capita floor area or material turnover will lead to a considerable increase in impacts. The new modeling approach overcomes the limitations of previous bottom-up building models and allows for investigating building material flows and stocks in space and time. This supports the development of tailored strategies to reduce the material footprint and environmental impacts of buildings and settlements.ISSN:1088-1980ISSN:1530-929
Radiocarbon Date List X: Baffin Bay, Baffin Island, Iceland, Labrador Sea, and the Northern North Atlantic
Date List X contains an annotated listing of 213 radiocarbon dates determined on samples from marine and terrestrial environments. The marine samples were collected from the East Greenland, Iceland, Spitzbergen, and Norwegian margins, Baffin Bay, and Labrador Sea. The terrestrial samples were collected from Vestfirdir, Iceland and Baffin Island. The samples were submitted by INSTAAR and researchers affiliated with INSTAAR\u27s Micropaleontology Laboratory under the direction of Dr.’s John T. Andrews and Anne E. Jennings. All of the dates from marine sediment cores were determined from either shells or foraminifera (both benthic and planktic). All dates were obtained by the Accelerator Mass Spectrometry (AMS) method. Regions of concentrated marine research include: Baffin Bay, Baffin Island, Labrador Sea, East Greenland fjords, shelf and slope, Denmark Strait, the southwestern and northwestern Iceland shelves, and Vestfirdir, Iceland. The non-marine radiocarbon dates are from peat, wood, plant microfossils, and mollusc. The radiocarbon dates have been used to address a variety of research objectives such as: 1. determining the timing of northern hemisphere high latitude environmental changes including glacier advance and retreat, and 2. assessing the accuracy of a fluctuating reservoir correction. Thus, most of the dates constrain the timing, rate, and interaction of late Quaternary paleoenvironmental fluctuations in sea level, glacier extent, sediment input, and changes in ocean circulation patterns. Where significant, stratigraphic and sample contexts are presented for each core to document the basis for interpretations
IEA EBC Annex 57 ‘Evaluation of Embodied Energy and CO<sub>2eq</sub> for Building Construction'
The current regulations to reduce energy consumption and greenhouse gas emissions (GHG) from buildings have focused on operational energy consumption. Thus legislation excludes measurement and reduction of the embodied energy and embodied GHG emissions over the building life cycle. Embodied impacts are a significant and growing proportion and it is increasingly recognized that the focus on reducing operational energy consumption needs to be accompanied by a parallel focus on reducing embodied impacts. Over the last six years the Annex 57 has addressed this issue, with researchers from 15 countries working together to develop a detailed understanding of the multiple calculation methods and the interpretation of their results. Based on an analysis of 80 case studies, Annex 57 showed various inconsistencies in current methodological approaches, which inhibit comparisons of results and difficult development of robust reduction strategies. Reinterpreting the studies through an understanding of the methodological differences enabled the cases to be used to demonstrate a number of important strategies for the reduction of embodied impacts. Annex 57 has also produced clear recommendations for uniform definitions and templates which improve the description of system boundaries, completeness of inventory and quality of data, and consequently the transparency of embodied impact assessments
Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine
Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant
Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations
Background: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case-control cohorts from Spain and Sweden, and a set of MS trio families from Finland. Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases.Peer Reviewe
Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.publishedVersio
Alterations of E-cadherin and β-catenin in gastric cancer
BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. METHODS: We studied the alterations of E-cadherin and β-catenin in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC). RESULTS: A high frequency (75%) of LOH was detected at 16q22.1 containing E-cadherin locus. Three cases (6%) showed the identical missense mutation, A592T. This mutation is not likely to contribute strongly to the carcinogenesis of gastric cancer, because a low frequency (1.6%) of this mutation was also found in 187 normal individuals. We also detected a low frequency (0.36%, 0%) of this mutation in 280 breast tumours and 444 other tumours, including colon and rectum, lung, endometrium, ovary, testis, kidney, thyroid carcinomas and sarcomas, respectively. We also analyzed the aberrant E-cadherin mRNAs in the gastric tumours and found that 7 tumours (18%) had aberrant mRNAs in addition to the normal mRNA. These aberrant mRNAs may produce abnormal E-cadherin molecules, resulting in weak cell-cell adhesion and invasive behaviour of carcinoma cells. Reduced expression of E-cadherin and β-catenin was identified at the frequency of 42% and 28%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for β-catenin IHC. An association was found between reduced expression of E-cadherin and β-catenin. Moreover, an association was detected between reduced expression of E-cadherin and diffuse histotype. CONCLUSION: Our results support the hypothesis that alterations of E-cadherin and β-catenin play a role in the initiation and progression of gastric cancer
Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders
<p>Abstract</p> <p>Background</p> <p>Few studies exist on the validity of food frequency questionnaires (FFQs) administered to elderly people. The aim of this study was to assess the validity of a short FFQ on present dietary intake, developed specially for the AGES-Reykjavik Study, which includes 5,764 elderly individuals. Assessing the validity of FFQs is essential before they are used in studies on diet-related disease risk and health outcomes.</p> <p>Method</p> <p>128 healthy elderly participants (74 y ± 5.7; 58.6% female) answered the AGES-FFQ, and subsequently filled out a 3-day weighed food record. Validity of the AGES-FFQ was assessed by comparing its answers to the dietary data obtained from the weighed food records, using Spearman's rank correlation, Chi-Square/Kendall's tau, and a Jonckheere-Terpstra test for trend.</p> <p>Result</p> <p>For men a correlation ≥ 0.4 was found for potatoes, fresh fruits, oatmeal/muesli, cakes/cookies, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee, tea and sugar in coffee/tea (r = 0.40-0.71). A lower, but acceptable, correlation was also found for raw vegetables (r = 0.33). The highest correlation for women was found for consumption of rye bread, oatmeal/muesli, raw vegetables, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee and tea (r = 0.40-0.61). An acceptable correlation was also found for fish topping/salad, fresh fruit, blood/liver sausage, whole-wheat bread, and sugar in coffee/tea (r = 0.28-0.37). Questions on meat/fish meals, cooked vegetables and soft drinks did not show a significant correlation to the reference method. Pearson Chi-Square and Kendall's tau showed similar results, as did the Jonckheere-Terpstra trend test.</p> <p>Conclusion</p> <p>A majority of the questions in the AGES-FFQ had an acceptable correlation and may be used to rank individuals according to their level of intake of several important foods/food groups. The AGES-FFQ on present diet may therefore be used to study the relationship between consumption of several specific foods/food groups and various health-related endpoints gathered in the AGES-Reykjavik Study.</p
Non-native hydrophobic interactions detected in unfolded apoflavodoxin by paramagnetic relaxation enhancement
Transient structures in unfolded proteins are important in elucidating the molecular details of initiation of protein folding. Recently, native and non-native secondary structure have been discovered in unfolded A. vinelandii flavodoxin. These structured elements transiently interact and subsequently form the ordered core of an off-pathway folding intermediate, which is extensively formed during folding of this α–β parallel protein. Here, site-directed spin-labelling and paramagnetic relaxation enhancement are used to investigate long-range interactions in unfolded apoflavodoxin. For this purpose, glutamine-48, which resides in a non-native α-helix of unfolded apoflavodoxin, is replaced by cysteine. This replacement enables covalent attachment of nitroxide spin-labels MTSL and CMTSL. Substitution of Gln-48 by Cys-48 destabilises native apoflavodoxin and reduces flexibility of the ordered regions in unfolded apoflavodoxin in 3.4 M GuHCl, because of increased hydrophobic interactions in the unfolded protein. Here, we report that in the study of the conformational and dynamic properties of unfolded proteins interpretation of spin-label data can be complicated. The covalently attached spin-label to Cys-48 (or Cys-69 of wild-type apoflavodoxin) perturbs the unfolded protein, because hydrophobic interactions occur between the label and hydrophobic patches of unfolded apoflavodoxin. Concomitant hydrophobic free energy changes of the unfolded protein (and possibly of the off-pathway intermediate) reduce the stability of native spin-labelled protein against unfolding. In addition, attachment of MTSL or CMTSL to Cys-48 induces the presence of distinct states in unfolded apoflavodoxin. Despite these difficulties, the spin-label data obtained here show that non-native contacts exist between transiently ordered structured elements in unfolded apoflavodoxin
Germline variants of ATG7 in familial cholangiocarcinoma alter autophagy and p62
Funding Information: The authors recognize and appreciate the patients and families who contributed to the current study. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the Icelandic cancer patients. We thank deCODE genetics for access to data and facilities, assistance with data analysis and helpful discussions. This work was supported by the National Institutes of Health [P01HG000205 to SUG and HPJ, 1U01CA15192001-A1 to HPJ, 1U01CA176299 to HPJ, HG006137-07 to HPJ, R01 CA116468NIH to DAJ, 5K08CA166512 to LDN]; Intermountain Healthcare to SUG, JC and HPJ; a Research Scholar Grant from the American Cancer Society [RSG-13-297-01-TBG to JC and HPJ]; Clayville Foundation to HPJ; Gastric Cancer Foundation to HPJ and LDN; the Samuel Waxman Cancer Research Foundation to DAJ; Oklahoma Center for Adult Stem Cell Research (OCASCR) to DAJ; Oklahoma Medical Research Foundation (OMRF) to DAJ; the Conquer Cancer Foundation (Young Investigator Award) to LDN; the Carl Kawaja Foundation to LDN; the Research Fund of Iceland [130230-0529 to ES and MHO, 184861-052 to ES, 184727-051 to MHO]; and a grant from the Icelandic Cancer Society Research Fund to MHO. Publisher Copyright: © 2022, The Author(s).Autophagy is a housekeeping mechanism tasked with eliminating misfolded proteins and damaged organelles to maintain cellular homeostasis. Autophagy deficiency results in increased oxidative stress, DNA damage and chronic cellular injury. Among the core genes in the autophagy machinery, ATG7 is required for autophagy initiation and autophagosome formation. Based on the analysis of an extended pedigree of familial cholangiocarcinoma, we determined that all affected family members had a novel germline mutation (c.2000C>T p.Arg659* (p.R659*)) in ATG7. Somatic deletions of ATG7 were identified in the tumors of affected individuals. We applied linked-read sequencing to one tumor sample and demonstrated that the ATG7 somatic deletion and germline mutation were located on distinct alleles, resulting in two hits to ATG7. From a parallel population genetic study, we identified a germline polymorphism of ATG7 (c.1591C>G p.Asp522Glu (p.D522E)) associated with increased risk of cholangiocarcinoma. To characterize the impact of these germline ATG7 variants on autophagy activity, we developed an ATG7-null cell line derived from the human bile duct. The mutant p.R659* ATG7 protein lacked the ability to lipidate its LC3 substrate, leading to complete loss of autophagy and increased p62 levels. Our findings indicate that germline ATG7 variants have the potential to impact autophagy function with implications for cholangiocarcinoma development.Peer reviewe
- …