Bacterial diversity and predicted enzymatic function in a multipurpose surface water system – from wastewater effluent discharges to drinking water production

Funding Information: The authors would like to express special acknowledgment to the CONPAT research team at the Finnish Institute for Health and Welfare, Finnish Environment Institute, and VATT Institute for Economic Research. Special thanks go to Tiina Heiskanen and Laura Wessels for extracting the nucleic acids. The Water Protection Association of the River Kokem?enjoki (KVVY) is acknowledged for surface water and wastewater sampling. Funding Information: Academy of Finland (grant number 263451) and Kaute Foundation (grant number 20190366) are acknowledged for providing funds for the project establishment and manuscript writing, respectively. Funding Information: The authors declare that they have no competing interests. This work was in part supported by the U.S. Environmental Protection Agency (EPA), and any opinions expressed do not reflect the views of the agency; therefore, no official endorsement should be inferred. Any mention of trade names or commercial products does not constitute endorsement or recommendation for use. Publisher Copyright: © 2021, The Author(s).Background Rivers and lakes are used for multiple purposes such as for drinking water (DW) production, recreation, and as recipients of wastewater from various sources. The deterioration of surface water quality with wastewater is well-known, but less is known about the bacterial community dynamics in the affected surface waters. Understanding the bacterial community characteristics -from the source of contamination, through the watershed to the DW production process-may help safeguard human health and the environment. Results The spatial and seasonal dynamics of bacterial communities, their predicted functions, and potential health-related bacterial (PHRB) reads within the Kokemaenjoki River watershed in southwest Finland were analyzed with the 16S rRNA-gene amplicon sequencing method. Water samples were collected from various sampling points of the watershed, from its major pollution sources (sewage influent and effluent, industrial effluent, mine runoff) and different stages of the DW treatment process (pre-treatment, groundwater observation well, DW production well) by using the river water as raw water with an artificial groundwater recharge (AGR). The beta-diversity analysis revealed that bacterial communities were highly varied among sample groups (R = 0.92, p = 13%) than in other groups (= 13%) than in others (Peer reviewe

The Role of Inflammatory Cytokines as Intermediates in the Pathway from Increased Adiposity to Disease

Objective This study aimed to investigate the role of cytokines as intermediates in the pathway from increased adiposity to disease.Methods BMI and circulating levels of up to 41 cytokines were measured in individuals from three Finnish cohort studies (n = 8,293). Mendelian randomization (MR) was used to assess the impact of BMI on circulating cytokines and the impact of BMI-driven cytokines on risk of obesity-related diseases. Results Observationally, BMI was associated with 19 cytokines. For every SD increase in BMI, causal effect estimates were strongest for hepatocyte growth factor, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and were as ratios of geometric means 1.13 (95% CI: 1.08-1.19), 1.08 (95% CI: 1.04-1.14), and 1.13 (95% CI: 1.04-1.21), respectively. TRAIL was associated with a small increase in the odds of coronary artery disease (odds ratio: 1.03; 95% CI: 1.00-1.06). There was inconsistent evidence for a protective role of MCP-1 against inflammatory bowel diseases.Conclusions Observational and MR estimates of the effect of BMI on cytokine levels were generally concordant. There was little evidence for an effect of raised levels of BMI-driven cytokines on disease. These findings illustrate the challenges of MR when applied in the context of molecular mediation.</p

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

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

Ajoneuvojen turvalaitteiden merkitys kuolemaan johtaneissa liikenneonnettomuuksissa

Tässä insinöörityössä tarkastellaan turvalaitteiden merkitystä henkilö- ja pakettiautoissa kuolemaan johtaneissa liikenneonnettomuuksissa. Tavoitteena oli selvittää, millaisilla turvalaitteilla onnettomuuksissa olleet ajoneuvot oli varustettu sekä mikä oli turvalaitteiden vaikutus onnettomuuksien seurausten kannalta. Lisäksi tavoitteena oli pohtia riskitekijöiden perusteella ajoneuvokohtaisia parannusehdotuksia. Työ toteutettiin yhteistyössä Liikennevakuutuskeskuksen liikenneturvallisuusyksikön henkilökunnan kanssa. Materiaaleina käytettiin Liikenneonnettomuuksien tutkijalautakuntien tutkimien kuolemaan johtaneiden onnettomuuksien vuodelta 2010 kerättyä tutkinta-aineistoa. Tutkinta-aineistosta on satunnaisesti valittu 25 tapausta, joita tarkastellaan työssä yksitellen. Tapauksista on kerrottu avaintapahtumat ja perustiedot, riskitekijät ja parannusehdotukset. Tiedot on taulukoitu ja ajoneuvoista on esitetty onnettomuustietoihin perustuva turvallisuusluokitus. Lisäksi turvalaitteiden merkityksellisyys, riskitekijät ja onnettomuuksien estomahdollisuudet tutkituissa onnettomuuksissa on esitetty kuvaajilla. Tuloksista nähdään, millaisista riskitekijöistä ja ajoneuvon puutteista vakavat liikenneon-nettomuudet syntyvät. Insinöörityön tuloksena saatiin luotettavaa tietoa ajoneuvokannan turvallisuustasosta. Työ antaa myös käsityksen siitä, mihin turvallisuusasioihin valmistajien tulisi jatkossa panostaa.The objective of this Bachelor’s thesis in engineering was to review the importance of safety devices in passenger cars and vans in fatal traffic accidents. The aim was to find out with what kind of safety devices the vehicles were equipped, and what impact the safety devices had in the accidents. Also the aim was to consider the risk factors on the basis of suggestions for improvement in vehicles. This thesis was assigned by the staff from the Road Safety Unit of the Finnish Motor Insurers´ Centre. The investigation files of the Finnish Motor Insurers’ Centre which have been gathered from the year 2010 were used as source material. 25 accidents were selected randomly and they are described one by one. After that the main findings, basic information, risk factors and suggestions for improvement are described. The data are tabulated and vehicles are presented in the accidents based on the information security classification. In addition, the impact of safety devices, risk factors and opportunities for prevention accidents are presented in graphs. The results of the thesis show what kind of risk factors and vehicle deficiencies cause traffic accidents. As the results of this Bachelor’s thesis were obtained reliable information about level of safety in vehicle fleet. This thesis should help the vehicle manufacturers to continue to invest in the development of safety issues

Why did the perfect marriage end : case Cloetta Fazer

Mergers are often used purposeful strategic tool. Previous research has mainly concentrated on actu-al M&A process and to elements leading to that decision. Purpose of this study is to approach de-merger of Cloetta Fazer and research what were the reasons that lead to demerger. Problem is ap-proached by first evaluating was the merger an success in the first place, as described in earlier stud-ies, media and academic research. From this information the motives for demerger are approached. Research material for study is collected from second hand sources. Research data-sample was di-vided into two categories: Timeline Sample & Additional Information Sample. Timeline sample was collected by systematically collecting news from Sanoma News database and Alma News database. This data was indexed and a timeline was constructed. From this timeline key dates, themes and elements were identified and further data gathering was concentrated based on those themes. Results of the study suggest that Merger was not as great success as it was described in earlier years. Explanations why merger ended up into demerger vary greatly. From material key factor, lack of, or error in, long term strategic planning was identified. This was due to death in family during strategy creation and mistakes made in pre-merger phase.siirretty Doriast