Towards quantitative ecology : Newton’s principia revisited

Peer reviewe

A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at- onset informed approach

Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10−7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05–1.32); meta-analysis p = 2.6×10−8). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10−15; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS.Public Library of Science open acces

Gereja Dan Kemiskinan: Diskursus Peran Gereja Di Tengah Kemiskinan

Fibry Jati Nugroho, Church and Poverty: Discourse on the Role of the Church in the Midst of Poverty. The problem of poverty is not only a local problem, but a problem that the world is struggling with. The Church as the Lord's mandate in the middle of the world, is required to play a role in helping the problem of poverty. How naturally does the church play a role in the midst of community poverty? By using descriptive analysis methods, and in conjunction with the thinking of Karl Marx, examine the role of the church in helping to overcome the problem of poverty. The church's calling should be to voice injustice and oppression of poor people's rights. The Church is present to side with the weak, the powerless, the poor, and the marginalized. If the church does not have partiality to the weak, then the presence of the church has no meaning. The church needs to continually offer its prophetic criticism indiscriminately against various abuses of power, the occurrence of injustice, the deprivation of public rights, and the oppressive and impoverishing system of humans. The spirituality and religiosity of the congregation must also come to a social piety, in which the spiritual energy possessed by the congregation is able to encourage concern for various problems in people's lives. Spirituality like this must be a concern of the church in building the life of the church. The cross must be understood as a reflection of the suffering and death of Christ, but at the same time must be able to open the eyes and ears of suffering, misery, and human hope for their dignity and human dignity. That's where the church plays a role. Fibry Jati Nugroho, Gereja dan Kemiskinan: Diskursus Peran Gereja di Tengah Kemiskinan. Permasalahan kemiskinan bukan hanya menjadi masalah lokal, namun menjadi masalah yang digumulkan oleh dunia. Gereja sebagai mandataris Tuhan di tengah dunia, dituntut untuk dapat berperan dalam membantu masalah kemiskinan. Bagaimanakah sewajarnya gereja berperan di tengah kemiskinan masyarakat? Dengan menggunakan metode deskriptif analisis, serta meminjam pemikiran Karl Marx, untuk menelisik peran gereja dalam membantu mengatasi permasalahan kemiskinan. Panggilan gereja yang seharusnya adalah untuk menyuarakan ketidakadilan dan penindasan hak-hak orang mis­kin.  Gereja hadir untuk berpihak kepada yang lemah, tidak ber­daya, miskin, dan yang terpinggirkan. Jika gereja tidak memiliki keperpihakan kepada yang lemah, maka kehadiran gereja tidak memiliki makna. Gereja perlu terus menerus menyu­ara­kan kritik profetisnya tanpa pandang bulu terhadap berbagai penyalah­gunaan kekuasaan, terjadinya ketidakadilan, terampasnya hak-hak masya­rakat, dan terhadap sistim yang menindas serta memiskinkan manusia. Spiritualitas dan religiusitas jemaat juga harus sampai kepada sebuah kesalehan sosial, di mana energi spiritual yang dimiliki jemaat mampu untuk mendorong kepeduliannya akan berbagai persoalan kehidupan masyarakat. Spiritualitas seperti inilah yang harus menjadi perhatian gereja dalam membangun kehidupan jemaat. Salib harus dipahami sebagai refleksi atas penderitaan dan kematian Kristus, namun di saat yang sama pula harus mampu membuka mata dan telinga akan penderitaan, kesengsaraan, dan pengharapan manusia akan harkat dan martabatnya sebagai manusia. Disitulah gereja berperan

Puutavaranmittauksen neuvottelukunnan kokous 1/2021

Pöytäkirjaluonnos 25.2.2021. Hyväksytään 3.6.202

Puutavaranmittauksen neuvottelukunnan kokous 1/2020

Pöytäkirja 27.3.2020. Hyväksytty 8.9.202

Puutavaranmittauksen neuvottelukunnan kokous 2/2020

Pöytäkirja 21.9.2020. Hyväksytty 16.2.2021

Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality

Aims The purpose of this study was to identify novel genetic variants influencing circulating asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and to evaluate whether they have a prognostic value on cardiovascular mortality. Methods and results We conducted a genome-wide association study on the methylarginine traits and investigated the predictive value of the new discovered variants on mortality. Our meta-analyses replicated the previously known locus for ADMA levels in DDAH1 (rs997251; P = 1.4 × 10−40), identified two non-synomyous polymorphisms for SDMA levels in AGXT2 (rs37369; P = 1.4 × 10−40 and rs16899974; P = 1.5 × 10−38) and one in SLC25A45 (rs34400381; P = 2.5 × 10−10). We also fine-mapped the AGXT2 locus for further independent association signals. The two non-synonymous AGXT2 variants independently associated with SDMA levels were also significantly related with short-term heart rate variability (HRV) indices in young adults. The major allele (C) of the novel non-synonymous rs16899974 (V498L) variant associated with decreased SDMA levels and an increase in the ratio between the low- and high-frequency spectral components of HRV (P = 0.00047). Furthermore, the SDMA decreasing allele (G) of the non-synomyous SLC25A45 (R285C) variant was associated with a lower resting mean heart rate during the HRV measurements (P = 0.0046), but not with the HRV indices. None of the studied genome-wide significant variants had any major effect on cardiovascular or total mortality in patients referred for coronary angiography. Conclusions AGXT2 has an important role in SDMA metabolism in humans. AGXT2 may additionally have an unanticipated role in the autonomic nervous system regulation of cardiac functio

The Center of Excellence in Atmospheric Science (2002–2019) — from molecular and biological processes to the global climate

The study of atmospheric processes related to climate requires a multidisciplinary approach, encompassing physics, chemistry, meteorology, forest science, and environmental science. The Academy of Finland Centre of Excellence in atmospheric sciences (CoE ATM) responded to that need for 18 years and produced extensive research and eloquent results, which are summarized in this review. The work in the CoE ATM enhanced our understanding in biogeochemical cycles, ecosystem processes, dynamics of aerosols, ions and neutral clusters in the lower atmosphere, and cloud formation and their interactions and feedbacks. The CoE ATM combined continuous and comprehensive long-term in-situ observations in various environments, ecosystems and platforms, ground- and satellitebased remote sensing, targeted laboratory and field experiments, and advanced multi-scale modeling. This has enabled improved conceptual understanding and quantifications across relevant spatial and temporal scales. Overall, the CoE ATM served as a platform for the multidisciplinary research community to explore the interactions between the biosphere and atmosphere under a common and adaptive framework

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe

Ateroskleroosin, iskeemisen aivoverenkiertohäiriön ja LDL:n hapettumisen geneettinen tausta: HDAC9 ja MMP12 geenien merkitys

Ateroskleroosista eli valtimonkovettumataudista johtuvat sydän- ja verisuonitaudit aiheuttavat suurimman osan kuolemista ja sairastuvuudesta länsimaissa. Hapettunutta ”low-density” –lipoproteiinia (oxLDL) pidetään olennaisena riskitekijänä ateroskleroosin tautiprosessissa. Ateroskleroosivaurion repeämä ja sitä seuraava veritulppa voivat aiheuttaa esimerkiksi sydäninfarktin, sydänperäisen äkkikuoleman tai iskeemisen aivoverenkiertohäiriön. Tässä tutkimuksessa käytimme koko genomin laajuista lähestymistapaa useassa laajassa potilasaineistossa. Geenien vaikutusta ateroskleroosiin tutkittiin leikkauksen yhteydessä otetuissa ateroskleroottisissa verisuoninäytteissä. Tarkoituksenamme oli löytää uusia geenejä tai niiden geenivariantteja, jotka vaikuttavat ateroskleroosin ja iskeemisen aivoverenkiertohäiriön patogeneesiin sekä verenkierron oxLDL:n määrään. Löysimme uusia ateroskleroosin ja iskeemisen aivoverenkiertohäiriön riskiin sekä oxLDL-pitoisuuteen vaikuttavia geneettisiä tekijöitä. HDAC9 edistää kaulasuonen ateroskleroosia. HDAC9 ja MMP12 assosioituvat ateroskleroottisen plakin vakavuusasteeseen ja iskeemisen aivoverenkiertohäiriön riskiin. ApoB Pro2739Leu on uusi seerumin oxLDL-pitoisuuteen vaikuttava geenivariaatio.Background: Cardiovascular diseases (CVD) are the number one cause of death and morbidity in the modern world. Oxidized low-density lipoprotein (oxLDL) is considered to be a key factor in the development of atherosclerosis, which leads to CVD such as coronary artery disease (CAD) and ischemic stroke. We used genome-wide association (GWAS) and genome-wide expression approaches in order to find novel genes and their genetic variants associated with the pathogenesis and risk factors of atherosclerosis, ischemic stroke and circulatory oxLDL concentrations. Aims of the Study: 1) To find single nucleotide polymorphisms (SNP) associated with oxLDL by performing a GWAS on serum oxLDL-levels. 2) Study the association of the lead-SNP affecting LDL oxidation, rs676210 (apolipoprotein-B [apoB] Pro2739Leu), with the prevalence of CAD, MI and ischemic stroke. 3) Study the association of ischemic stroke risk increasing HDAC9 variants with carotid plaque prevalence and intima-media thickness (cIMT). 4) Find novel loci associated with ischemic stroke by performing an age-of-onset informed GWAS. 5) Study the expression of the found MMP12 gene and HDAC9 in clinically significant atherosclerotic arteries. 6) Study HDAC9 and MMP12 expression in relation to histologically determined severity of atherosclerotic plaques and gene markers for plaque stability, M1/M2 macrophages and smooth muscle cells. Materials and Methods: The artery samples used in the study were from Tampere Vascular Study (TVS, N=96, original communications III- V) and blood samples from the participants of the Young Finns Study (YFS, N=2080, I), the Ludwigshafen Risk and Cardiovascular Health (LURIC, study A, N=2913, with 271 cases and 2642 controls, I and II), Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study (B, N=1326, I), the Finnish Cardiovascular Study (FINCAVAS, N=1118, C, I), Angiography and Genes Study (ANGES, N=808, D, I), Wellcome Trust Case Control Consortium 2 (WTCCC2, E, N=3548 cases, 5972 controls, II- IV), CHARGE consortium (F, 25179 plaques and 31210 cIMT, III) and METASTROKE consortium (G, 6778 cases and 12095 controls, IV). Genotyping and imputation in all studies passed strict quality control (QC) measures. DNA (YFS and studies A-G) and mRNA (TVS) were isolated with appropriate commercial kits and the quality and integrity of RNA was closely examined. Serum levels of oxLDL were measured with Mercodia ELISA oxLDL assay (I and II). Statistical analyses were performed using PLINK, ProbABEL, PolyPhen-2 softwares and R statistical programming language. Results: In study I, the genetic variant rs676210 (Pro2739Leu) on apoB associated with oxLDL (p=4.3 x 10-136, effect size = 13.2 U/l per allele). Using PolyPhen-2 software Pro2739Leu was predicted to cause functional change in apoB protein structure. It did not associate significantly with CAD (hazard ratio [HR]=1.00 [0.94–1.06] per allele) or MI (HR=1.04 [0.96–1.12]). In study II, rs676210 associated with cerebrovascular disease events (p=0.030; odds ratio=1.29 [95% confidence interval 1.03‒1.63] for risk allele G). In study E, rs676210 did not associate with the history of ischemic stroke. In study III, both HDAC9 SNPs (rs11984041 and rs2107595) were associated with both common carotid IMT (p=0.00391 and p=0.0018, respectively) and with presence of carotid plaque (p=0.00425 and p=0.0022, respectively). HDAC9 staining was seen in the nuclei and cytoplasm of vascular smooth muscle cells, and in endothelial cells of cerebral and systemic arteries. In TVS, HDAC9 expression was upregulated in carotid plaques compared to atherosclerosis free controls (p=0.00000103). In study IV, we found novel MMP12 locus (rs660599) associated with ischemic stroke using an age-of-onset informed GWAS (p=2.5x10-7). In TVS, MMP12 gene was upregulated in atherosclerotic plaques compared to control vessels (fold change=336, p=1.2x10-15). In study V, HDAC9 and MMP12 expressions increased with plaque severity determined by American Heart Association classification (p=0.00018, and p<0.0001, for trend respectively) in all artery beds. HDAC9 expression correlated significantly with MMP12 expression in carotid plaques (r=0.46, p=0.012, N=29), and control samples (r=-0.44, p=0.034, N=28), but not in other artery beds. MMP12 expression showed positive correlation (p < 0.05) with 22% (2/9) M1 macrophage markers, and 79% (11/14) M2 macrophage markers, negative correlation with 72% (18/25) SMC markers, and no correlation with plaque stability markers in the carotid artery plaques. Conclusions: These results give novel insight into the genetic background of atherosclerosis, ischemic stroke and lipoprotein oxidation, and specifically indicate that apoB rs676210 (Pro2739Leu), HDAC9 and MMP12 related gene variations associate with the risk of ischemic stroke. HDAC9 variants may act via promoting atherosclerosis in the carotid artery. Both HDAC9 and MMP12 are overexpressed in atherosclerotic plaques and correlate with plaque severity. In addition, apoB Pro2739Leu is a novel genetic factor regulating circulatory oxLDL levels