Browsing by Subject "LANDSCAPE"

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  • Nikkanen, Joni; Landoni, Juan Cruz; Balboa, Diego; Haugas, Maarja; Partanen, Juha; Paetau, Anders; Isohanni, Pirjo; Brilhante, Virginia; Suomalainen, Anu (2018)
    DNA polymerase gamma (POLG), the mtDNA replicase, is a common cause of mitochondrial neurodegeneration. Why POLG defects especially cause central nervous system (CNS) diseases is unknown. We discovered a complex genomic regulatory locus for POLG, containing three functional CNS-specific enhancers that drive expression specifically in oculomotor complex and sensory interneurons of the spinal cord, completely overlapping with the regions showing neuronal death in POLG patients. The regulatory locus also expresses two functional RNAs, LINC00925-RNA and MIR9-3, which are coexpressed with POLG. The MIR9-3 targets include NR2E1, a transcription factor maintaining neural stem cells in undifferentiated state, and MTHFD2, the regulatory enzyme of mitochondrial folate cycle, linking POLG expression to stem cell differentiation and folate metabolism. Our evidence suggests that distant genomic non-coding regions contribute to regulation of genes encoding mitochondrial proteins. Such genomic arrangement of POLG locus, driving expression to CNS regions affected in POLG patients, presents a potential mechanism for CNS-specific manifestations in POLG disease.
  • Kaukonen, Maria; Quintero, Ileana B.; Mukarram, Abdul Kadir; Hytönen, Marjo K.; Holopainen, Saila; Wickström, Kaisa; Kyöstilä, Kaisa; Arumilli, Meharji; Jalomäki, Sari; Daub, Carsten O.; Kere, Juha; Lohi, Hannes; Consortium, the DoGA (2020)
    Author summary Retinitis pigmentosa (RP) is a blinding eye disease that affects nearly two million people worldwide. Several genes and variants have been associated with the disease, but still 30-80% of the patients lack genetic diagnosis. There is currently no standard treatment for RP, and much is expected from gene therapy. A similar disease, called progressive retinal atrophy (PRA), affects many dog breeds. We performed clinical, genetic and functional analyses to find the genetic cause for PRA in Miniature Schnauzers. We discovered two forms of PRA in the breed, named type 1 and 2, and show that they are genetically distinct as they map to different chromosomes, 15 and X, respectively. Further genetic, bioinformatic and functional analyses discovered a fully penetrant recessive variant in a putative silencer region for type 1 PRA. Silencer regions are important for gene regulation and we found that two of its predicted target genes, EDN2 and COL9A2, were overexpressed in the retina of the affected dog. Defects in both EDN2 and COL9A2 have been associated with retinal degeneration. This study provides new insights to retinal biology while the genetic test guides better breeding choices. Retinitis pigmentosa (RP) is the leading cause of blindness with nearly two million people affected worldwide. Many genes have been implicated in RP, yet in 30-80% of the RP patients the genetic cause remains unknown. A similar phenotype, progressive retinal atrophy (PRA), affects many dog breeds including the Miniature Schnauzer. We performed clinical, genetic and functional experiments to identify the genetic cause of PRA in the breed. The age of onset and pattern of disease progression suggested that at least two forms of PRA, types 1 and 2 respectively, affect the breed, which was confirmed by genome-wide association study that implicated two distinct genomic loci in chromosomes 15 and X, respectively. Whole-genome sequencing revealed a fully segregating recessive regulatory variant in type 1 PRA. The associated variant has a very recent origin based on haplotype analysis and lies within a regulatory site with the predicted binding site of HAND1::TCF3 transcription factor complex. Luciferase assays suggested that mutated regulatory sequence increases expression. Case-control retinal expression comparison of six best HAND1::TCF3 target genes were analyzed with quantitative reverse-transcriptase PCR assay and indicated overexpression of EDN2 and COL9A2 in the affected retina. Defects in both EDN2 and COL9A2 have been previously associated with retinal degeneration. In summary, our study describes two genetically different forms of PRA and identifies a fully penetrant variant in type 1 form with a possible regulatory effect. This would be among the first reports of a regulatory variant in retinal degeneration in any species, and establishes a new spontaneous dog model to improve our understanding of retinal biology and gene regulation while the affected breed will benefit from a reliable genetic testing.
  • Kucuk, Can; Jiang, Bei; Hu, Xiaozhou; Zhang, Wenyan; Chan, John K. C.; Xiao, Wenming; Lack, Nathan; Alkan, Can; Williams, John C.; Avery, Kendra N.; Kavak, Pinar; Scuto, Anna; Sen, Emel; Gaulard, Philippe; Staudt, Lou; Iqbal, Javeed; Zhang, Weiwei; Cornish, Adam; Gong, Qiang; Yang, Qunpei; Sun, Hong; d'Amore, Francesco; Leppa, Sirpa; Liu, Weiping; Fu, Kai; de Leval, Laurence; McKeithan, Timothy; Chan, Wing C. (2015)
  • Cervera-Carrascon, Victor; Quixabeira, Dafne C. A.; Santos, Joao M.; Havunen, Riikka; Milenova, Ioanna; Verhoeff, Jan; Heinio, Camilla; Zafar, Sadia; Garcia-Vallejo, Juan J.; van Beusechem, Victor W.; de Gruijl, Tanja D.; Kalervo, Aino; Sorsa, Suvi; Kanerva, Anna; Hemminki, Akseli (2021)
    Immune checkpoint inhibitors such as anti-PD-1 have revolutionized the field of oncology over the past decade. Nevertheless, the majority of patients do not benefit from them. Virotherapy is a flexible tool that can be used to stimulate and/or recruit different immune populations. T-cell enabling virotherapy could enhance the efficacy of immune checkpoint inhibitors, even in tumors resistant to these inhibitors. The T-cell potentiating virotherapy used here consisted of adenoviruses engineered to express tumor necrosis factor alpha and interleukin-2 in the tumor microenvironment. To study virus efficacy in checkpoint-inhibitor resistant tumors, we developed an anti-PD-1 resistant melanoma model in vivo. In resistant tumors, adding virotherapy to an anti-PD-1 regimen resulted in increased survival (p=0.0009), when compared to anti-PD-1 monotherapy. Some of the animals receiving virotherapy displayed complete responses, which did not occur in the immune checkpoint-inhibitor monotherapy group. When adenoviruses were delivered into resistant tumors, there were signs of increased CD8 T-cell infiltration and activation, which - together with a reduced presence of M2 macrophages and myeloid-derived suppressor cells - could explain those results. T-cell enabling virotherapy appeared as a valuable tool to counter resistance to immune checkpoint inhibitors. The clinical translation of this approach could increase the number of cancer patients benefiting from immunotherapies.
  • Haider, Zahra; Larsson, Pär; Landfors, Mattias; Köhn, Linda; Schmiegelow, Kjeld; Flægstad, Trond; Kanerva, Jukka; Heyman, Mats; Hultdin, Magnus; Degerman, Sofie (2019)
    Classification of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T-ALL patients were characterized by genome-wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P <0.001) and mitotic age (P <0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2-1, and novel genes in T-ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP- subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL-TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP-), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T-ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.
  • Tolvanen, Jere; Pakanen, Veli-Matti; Valkama, Jari; Tornberg, Risto (2017)
    Capsule: Mark-recapture data suggest low apparent survival and sex- and population-specific site fidelity and territory turnover in adult Northern Goshawks Accipiter gentilis breeding in northern Europe.Aims: To understand how species cope with global environmental change requires knowledge of variation in population demographic rates, especially from populations close to the species' northern range limit and from keystone species such as raptors. We analyse apparent survival and breeding dispersal propensity of adult Northern Goshawks breeding in northern Europe.Methods: We used long-term mark-recapture data from two populations in Finland, northern Europe, and Cormack-Jolly-Seber models and binomial generalized linear models to investigate sex- and population-specific variation in apparent survival, territory turnover and site fidelity.Results: We report low apparent survival (53-72%) of breeding adult Goshawks. Breeding dispersal propensity was higher in females than males, especially in northern Finland, contrasting with previous studies that suggest high site fidelity in both sexes.Conclusion: Low apparent survival in females may be mainly due to permanent emigration outside the study areas, whereas in males the survival rate may truly be low. Both demographic aspects may be driven by the combination of sex-specific roles related to breeding and difficult environmental conditions prevailing in northern latitudes during the non-breeding season.
  • Vauhkonen, Jari; Ruotsalainen, Roope (2017)
    Determining optimal forest management to provide multiple goods and services, also referred to as Ecosystem Services (ESs), requires operational-scale information on the suitability of the forest for the provisioning of various ESs. Remote sensing allows wall-to-wall assessments and provides pixel data for a flexible composition of the management units. The purpose of this study was to incorporate models of ES provisioning potential in a spatial prioritization framework and to assess the pixel-level allocation of the land use. We tessellated the forested area in a landscape of altogether 7500 ha to 27,595 pixels of 48 x 48 m(2) and modeled the potential of each pixel to provide biodiversity, timber, carbon storage, and recreational amenities as indicators of supporting, provisioning, regulating, and cultural ESs, respectively. We analyzed spatial overlaps between the individual ESs, the potential to provide multiple ESs, and tradeoffs due to production constraints in a fraction of the landscape. The pixels considered most important for the individual ESs overlapped as much as 78% between carbon storage and timber production and up to 52.5% between the other ESs. The potential for multiple ESs could be largely explained in terms of forest structure as being emphasized to sparsely populated, spruce-dominated old forests with large average tree size. Constraining the production of the ESs in the landscape based on the priority maps, however, resulted in sub-optimal choices compared to an optimized production. Even though the land-use planning cannot be completed without involving the stakeholders' preferences, we conclude that the workflow described in this paper produced valuable information on the overlaps and tradeoffs of the ESs for the related decision support. (C) 2016 Elsevier B.V. All rights reserved.
  • Gaultier, Simon; Blomberg, Anna; Ijäs, Asko; Vasko, Ville Veijo Wilhelm; Vesterinen, Eero; Brommer, Jon Egbert; Lilley, Thomas M. (2020)
    Although labeled as environmentally friendly, wind power can have negative impacts on the environment, such as habitat destruction or wildlife fatalities. Considering the distribution and migratory characteristics of European bats, the negative effects of wind power should be addressed on an appropriate scale. This review summarizes the current state of knowledge on interactions between wind farms and bats in Europe, and compares it with the situation in the countries of the European boreal biogeographic region. We analyzed data from papers published in international and national scientific journals, focusing on studies conducted in Europe. The issue of the impacts wind power has on bats is clearly overlooked in most of the countries of the European boreal region, with low volumes of research available on the topic. This is probably due to fewer wind farms in the area, making this recent issue a less-prioritized topic. However, the Baltic Sea, and the countries surrounding it, are of extreme importance with regards to bat migration, especially for the Pipistrellus nathusii. Therefore, more research on wind power and bats is needed in this region, as well as more cooperation between all the stakeholders.
  • Teucher, Mike; Schmitt, Christine B.; Wiese, Anja; Apfelbeck, Beate; Maghenda, Marianne; Pellikka, Petri; Lens, Luc; Habel, Jan Christian (2020)
    Habitat destruction and deterioration are amongst the main drivers of biodiversity loss. Increasing demand for agricultural products, timber and charcoal has caused the rapid destruction of natural forests, especially in the tropics. The Taita Hills in southern Kenya are part of the Eastern Afromontane Biodiversity Hotspot and represent a highly diverse cloud forest ecosystem. However, the cloud forest suffers extremely from wood and timber exploitation and transformation into exotic tree plantations and agricultural fields. Existing conservation regulations and moratoriums aim to prevent further forest destruction. In this study, we analyzed land cover change and shifts in landscape configuration for a fraction of the Taita Hills, based on satellite imageries for the years 2003, 2011 and 2018. We found that the coverage of natural cloud forest further decreased between 2003 and 2018, despite the effort to conserve the remaining cloud forest patches and to reforest degraded areas by various conservation and management initiatives. In parallel, the proportion of exotic tree plantations and bushland strongly increased. Moreover, mean natural forest patch size decreased and the degree of interspersion with other land cover types increased notably. Logging bans for indigenous trees seem to have resulted in local opposition to the planting of indigenous trees and thereby hindered the recovering of the cloud forest. We suggest to enhance local awareness on the ecological value of the natural forest by community-based Conservation Forest Associations and to encourage the planting of indigenous tree species in farmer-owned woodlots. Besides, bottom-up management systems that allow for local participation in decision-making and benefit-sharing related to forest resources would be a way forward to achieve the sustainable use and conservation of the last remaining natural forest patches in the Taita Hills. (C) 2020 The Authors. Published by Elsevier B.V.
  • Koskenvuo, Juha W.; Saarinen, Inka; Ahonen, Saija; Tommiska, Johanna; Weckström, Sini; Seppala, Eija H.; Tuupanen, Sari; Kangas-Kontio, Tiia; Schleit, Jennifer; Helio, Krista; Hathaway, Julie; Gummesson, Anders; Dahlberg, Pia; Ojala, Tiina H.; Vepsäläinen, Ville; Kytola, Ville; Muona, Mikko; Sistonen, Johanna; Salmenpera, Pertteli; Gentile, Massimiliano; Paananen, Jussi; Myllykangas, Samuel; Alastalo, Tero-Pekka; Heliö, Tiina (2021)
    Background Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. Methods and results We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.
  • Koskenvuo, Juha W.; Saarinen, Inka; Ahonen, Saija; Tommiska, Johanna; Weckström, Sini; Seppala, Eija H.; Tuupanen, Sari; Kangas-Kontio, Tiia; Schleit, Jennifer; Helio, Krista; Hathaway, Julie; Gummesson, Anders; Dahlberg, Pia; Ojala, Tiina H.; Vepsäläinen, Ville; Kytola, Ville; Muona, Mikko; Sistonen, Johanna; Salmenpera, Pertteli; Gentile, Massimiliano; Paananen, Jussi; Myllykangas, Samuel; Alastalo, Tero-Pekka; Heliö, Tiina (2021)
    Background Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. Methods and results We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.
  • Abdi, Abdulhakim; Carrié, Romain; Sidemo-Holm, William; Cai, Zhanzhang; Boke Olén, Niklas; Smith, Henrik G; Eklundh, Lars; Ekroos, Johan Edvard (2021)
    Increasing land-use intensity is a main driver of biodiversity loss in farmland, but measuring proxies for land-use intensity across entire landscapes is challenging. Here, we develop a novel method for the assessment of the impact of land-use intensity on biodiversity in agricultural landscapes using remote sensing parameters derived from the Sentinel-2 satellites. We link crop phenology and productivity parameters derived from time-series of a two-band enhanced vegetation index with biodiversity indicators (insect pollinators and insect-pollinated vascular plants) in agricultural fields in southern Sweden, with contrasting land management (i.e. conventional and organic farming). Our results show that arable land-use intensity in cereal systems dominated by spring-sown cereals can be approximated using Sentinel-2 productivity parameters. This was shown by the significant positive correlations between the amplitude and maximum value of the enhanced vegetation index on one side and farmer reported yields on the other. We also found that conventional cereal fields had 17% higher maximum and 13% higher amplitude of their enhanced vegetation index than organic fields. Sentinel-2 derived parameters were more strongly correlated with the abundance and species richness of bumblebees and the richness of vascular plants than the abundance and species richness of butterflies. The relationships we found between biodiversity and crop production proxies are consistent with predictions that increasing agricultural land-use intensity decreases field biodiversity. The newly developed method based on crop phenology and productivity parameters derived from Sentinel-2 data serves as a proof of concept for the assessment of the impact of land-use intensity on biodiversity over cereal fields across larger areas. It enables the estimation of arable productivity in cereal systems, which can then be used by ecologists and develop tools for land managers as a proxy for land-use intensity. Coupled with spatially explicit databases on agricultural land-use, this method will enable crop-specific cereal productivity estimation across large geographical regions.
  • Menden, Michael P.; Wang, Dennis; Mason, Mike J.; Szalai, Bence; Bulusu, Krishna C.; Guan, Yuanfang; Yu, Thomas; Kang, Jaewoo; Jeon, Minji; Wolfinger, Russ; Nguyen, Tin; Zaslavskiy, Mikhail; Abante, Jordi; Abecassis, Barbara Schmitz; Aben, Nanne; Aghamirzaie, Delasa; Aittokallio, Tero; Akhtari, Farida S.; Al-lazikani, Bissan; Alam, Tanvir; Allam, Amin; Allen, Chad; de Almeida, Mariana Pelicano; Altarawy, Doaa; Alves, Vinicius; Amadoz, Alicia; Anchang, Benedict; Antolin, Albert A.; Ash, Jeremy R.; Aznar, Victoria Romeo; Ba-alawi, Wail; Bagheri, Moeen; Bajic, Vladimir; Ball, Gordon; Ballester, Pedro J.; Baptista, Delora; Bare, Christopher; Bateson, Mathilde; Bender, Andreas; Bertrand, Denis; Wijayawardena, Bhagya; Boroevich, Keith A.; Bosdriesz, Evert; Bougouffa, Salim; Bounova, Gergana; Brouwer, Thomas; Bryant, Barbara; Calaza, Manuel; Calderone, Alberto; Calza, Stefano; Capuzzi, Stephen; Carbonell-Caballero, Jose; Carlin, Daniel; Carter, Hannah; Castagnoli, Luisa; Celebi, Remzi; Cesareni, Gianni; Chang, Hyeokyoon; Chen, Guocai; Chen, Haoran; Chen, Huiyuan; Cheng, Lijun; Chernomoretz, Ariel; Chicco, Davide; Cho, Kwang-Hyun; Cho, Sunghwan; Choi, Daeseon; Choi, Jaejoon; Choi, Kwanghun; Choi, Minsoo; Cock, Martine De; Coker, Elizabeth; Cortes-Ciriano, Isidro; Cserzö, Miklós; Cubuk, Cankut; Curtis, Christina; Daele, Dries Van; Dang, Cuong C.; Dijkstra, Tjeerd; Dopazo, Joaquin; Draghici, Sorin; Drosou, Anastasios; Dumontier, Michel; Ehrhart, Friederike; Eid, Fatma-Elzahraa; ElHefnawi, Mahmoud; Elmarakeby, Haitham; van Engelen, Bo; Engin, Hatice Billur; de Esch, Iwan; Evelo, Chris; Falcao, Andre O.; Farag, Sherif; Fernandez-Lozano, Carlos; Fisch, Kathleen; Flobak, Asmund; Fornari, Chiara; Foroushani, Amir B. K.; Fotso, Donatien Chedom; Fourches, Denis; Friend, Stephen; Frigessi, Arnoldo; Gao, Feng; Gao, Xiaoting; Gerold, Jeffrey M.; Gestraud, Pierre; Ghosh, Samik; Gillberg, Jussi; Godoy-Lorite, Antonia; Godynyuk, Lizzy; Godzik, Adam; Goldenberg, Anna; Gomez-Cabrero, David; Gonen, Mehmet; de Graaf, Chris; Gray, Harry; Grechkin, Maxim; Guimera, Roger; Guney, Emre; Haibe-Kains, Benjamin; Han, Younghyun; Hase, Takeshi; He, Di; He, Liye; Heath, Lenwood S.; Hellton, Kristoffer H.; Helmer-Citterich, Manuela; Hidalgo, Marta R.; Hidru, Daniel; Hill, Steven M.; Hochreiter, Sepp; Hong, Seungpyo; Hovig, Eivind; Hsueh, Ya-Chih; Hu, Zhiyuan; Huang, Justin K.; Huang, R. Stephanie; Hunyady, László; Hwang, Jinseub; Hwang, Tae Hyun; Hwang, Woochang; Hwang, Yongdeuk; Isayev, Olexandr; Don’t Walk, Oliver Bear; Jack, John; Jahandideh, Samad; Ji, Jiadong; Jo, Yousang; Kamola, Piotr J.; Kanev, Georgi K.; Karacosta, Loukia; Karimi, Mostafa; Kaski, Samuel; Kazanov, Marat; Khamis, Abdullah M.; Khan, Suleiman Ali; Kiani, Narsis A.; Kim, Allen; Kim, Jinhan; Kim, Juntae; Kim, Kiseong; Kim, Kyung; Kim, Sunkyu; Kim, Yongsoo; Kim, Yunseong; Kirk, Paul D. W.; Kitano, Hiroaki; Klambauer, Gunter; Knowles, David; Ko, Melissa; Kohn-Luque, Alvaro; Kooistra, Albert J.; Kuenemann, Melaine A.; Kuiper, Martin; Kurz, Christoph; Kwon, Mijin; van Laarhoven, Twan; Laegreid, Astrid; Lederer, Simone; Lee, Heewon; Lee, Jeon; Lee, Yun Woo; Lepp_aho, Eemeli; Lewis, Richard; Li, Jing; Li, Lang; Liley, James; Lim, Weng Khong; Lin, Chieh; Liu, Yiyi; Lopez, Yosvany; Low, Joshua; Lysenko, Artem; Machado, Daniel; Madhukar, Neel; Maeyer, Dries De; Malpartida, Ana Belen; Mamitsuka, Hiroshi; Marabita, Francesco; Marchal, Kathleen; Marttinen, Pekka; Mason, Daniel; Mazaheri, Alireza; Mehmood, Arfa; Mehreen, Ali; Michaut, Magali; Miller, Ryan A.; Mitsopoulos, Costas; Modos, Dezso; Moerbeke, Marijke Van; Moo, Keagan; Motsinger-Reif, Alison; Movva, Rajiv; Muraru, Sebastian; Muratov, Eugene; Mushthofa, Mushthofa; Nagarajan, Niranjan; Nakken, Sigve; Nath, Aritro; Neuvial, Pierre; Newton, Richard; Ning, Zheng; Niz, Carlos De; Oliva, Baldo; Olsen, Catharina; Palmeri, Antonio; Panesar, Bhawan; Papadopoulos, Stavros; Park, Jaesub; Park, Seonyeong; Park, Sungjoon; Pawitan, Yudi; Peluso, Daniele; Pendyala, Sriram; Peng, Jian; Perfetto, Livia; Pirro, Stefano; Plevritis, Sylvia; Politi, Regina; Poon, Hoifung; Porta, Eduard; Prellner, Isak; Preuer, Kristina; Pujana, Miguel Angel; Ramnarine, Ricardo; Reid, John E.; Reyal, Fabien; Richardson, Sylvia; Ricketts, Camir; Rieswijk, Linda; Rocha, Miguel; Rodriguez-Gonzalvez, Carmen; Roell, Kyle; Rotroff, Daniel; de Ruiter, Julian R.; Rukawa, Ploy; Sadacca, Benjamin; Safikhani, Zhaleh; Safitri, Fita; Sales-Pardo, Marta; Sauer, Sebastian; Schlichting, Moritz; Seoane, Jose A.; Serra, Jordi; Shang, Ming-Mei; Sharma, Alok; Sharma, Hari; Shen, Yang; Shiga, Motoki; Shin, Moonshik; Shkedy, Ziv; Shopsowitz, Kevin; Sinai, Sam; Skola, Dylan; Smirnov, Petr; Soerensen, Izel Fourie; Soerensen, Peter; Song, Je-Hoon; Song, Sang Ok; Soufan, Othman; Spitzmueller, Andreas; Steipe, Boris; Suphavilai, Chayaporn; Tamayo, Sergio Pulido; Tamborero, David; Tang, Jing; Tanoli, Zia-ur-Rehman; Tarres-Deulofeu, Marc; Tegner, Jesper; Thommesen, Liv; Tonekaboni, Seyed Ali Madani; Tran, Hong; Troyer, Ewoud De; Truong, Amy; Tsunoda, Tatsuhiko; Turu, Gábor; Tzeng, Guang-Yo; Verbeke, Lieven; Videla, Santiago; Consortium, AstraZeneca-Sanger Drug Combination DREAM (2019)
    The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
  • Abrego, Nerea; Garcia-Baquero, Gonzalo; Halme, Panu; Ovaskainen, Otso; Salcedo, Isabel (2014)
  • Di Minin, Enrico; Clements, Hayley Susan; Correia, Ricardo A.; Cortes Capano, Gonzalo; Fink, Christoph; Haukka, Anna; Hausmann, Anna; Kulkarni, Ritwik; Bradshaw, Corey (2021)
    The widespread activity of recreational hunting is proposed as a means of conserving nature and supporting livelihoods. However, recreational hunting-especially trophy hunting-has come under increasing scrutiny based on ethical concerns and the arguments that it can threaten species and fail to contribute meaningfully to local livelihoods. We provide an overview of the peer-reviewed literature on recreational hunting of terrestrial birds and mammals between 1953 and 2020 (> 1,000 papers). The most-studied species are large mammals from North America, Europe, and Africa. While there is extensive research on species' ecology to inform sustainable hunting practices, there is comparably little research on the role of local perceptions and institutions in determining socioeconomic and conservation outcomes. Evidence is lacking to answer the pressing questions of where and how hunting contributes to just and sustainable conservation efforts. We outline an agenda to build this evidence base through research that recognizes diverse social-ecological contexts.
  • Heldbjerg, Henning; Fox, Anthony D.; Lehikoinen, Aleksi; Sunde, Peter; Aunins, Ainars; Balmer, Dawn E.; Calvi, Gianpiero; Chodkiewicz, Tomasz; Chylarecki, Przemek; Escandell, Virginia; Foppen, Ruud; Gamero, Anna; Hristov, Iordan; Husby, Magne; Jiguet, Frederic; Kmecl, Primoz; Kalas, John A.; Lewis, Lesley J.; Lindstrom, Ake; Moshoj, Charlotte; Nellis, Renno; Paquet, Jean-Y; Portolou, Danae; Ridzon, Jozef; Schmid, Hans; Skorpilova, Jana; Szabo, Zoltan D.; Szep, Tibor; Teufelbauer, Norbert; Trautmann, Sven; van Turnhout, Chris; Vermouzek, Zdenek; Vorisek, Petr; Weiserbs, Anne (2019)
    The greatest loss of biodiversity in the EU has occurred on agricultural land. The Common Starling (Sturnus vulgaris) is one of the many numerous and widespread European farmland breeding bird species showing major population declines linked to European agricultural intensification. Here we present results based on monitoring data collected since 1975 in 24 countries to examine the influence of changing extent of grassland and cattle abundance (based on results of earlier studies showing the importance of lowland cattle grazed grassland for the species), wintering provenance and temperature on national breeding population trends of Starlings across Europe. Positive Starling population trends in Central-East Europe contrast with negative trends in North and West Europe. Based on this indicative approach, we found some support for the importance of cattle stock and no support for grassland, temperature or wintering provenance to explain Starling population trends in Europe. However, we acknowledge such a European-wide analysis may conceal regional differences in responses and suggest that currently accessible national land use datamight be insufficient to describe the detailed current changes in animal husbandry and grassland management that may be responsible for changes in food availability and hence breeding Starling abundance and their differences across Europe. Reviewing results from local studies relating Starling population trends to local agricultural change offer contradictory results, suggesting complex interacting processes at work. We recommend combining national datasets on demography, land-use/agricultural practices and from autecological research to better explain the reasons for contrasting Starling trends across Europe, to enable us to predict how changing agriculture will affect Starlings and potentially suggest mitigation measures to restore local populations where possible.
  • Pradhan, Barun; Cajuso, Tatiana; Katainen, Riku; Sulo, Paivi; Tanskanen, Tomas; Kilpivaara, Outi; Pitkanen, Esa; Aaltonen, Lauri A.; Kauppi, Liisa; Palin, Kimmo (2017)
    Long interspersed nuclear elements-1 (L1s) are a large family of retrotransposons. Retrotransposons are repetitive sequences that are capable of autonomous mobility via a copy-and-paste mechanism. In most copy events, only the L1 sequence is inserted, however, they can also mobilize the flanking non-repetitive region by a process known as 3' transduction. L1 insertions can contribute to genome plasticity and cause potentially tumorigenic genomic instability. However, detecting the activity of a particular source L1 and identifying new insertions stemming from it is a challenging task with current methodological approaches. We developed a long-distance inverse PCR (LDI-PCR) based approach to monitor the mobility of active L1 elements based on their 3' transduction activity. LDI-PCR requires no prior knowledge of the insertion target region. By applying LDI-PCR in conjunction with Nanopore sequencing (Oxford Nanopore Technologies) on one L1 reported to be particularly active in human cancer genomes, we detected 14 out of 15 3' transductions previously identified by whole genome sequencing in two different colorectal tumour samples. In addition we discovered 25 novel highly subclonal insertions. Furthermore, the long sequencing reads produced by LDI-PCR/Nanopore sequencing enabled the identification of both the 5' and 3' junctions and revealed detailed insertion sequence information.
  • Saunaluoma, Sanna; Pärssinen, Martti; Schaan, Denise (2018)
    Amazonian earthworks, which are an important testimony to ancient anthropogenic landscape modifications, have a significant variety of structures and sizes, and are found in different geographical and ecological locations that indicate separate time periods, distinct cultural affiliations, and diverse purposes. We introduce data from diverse archaeological earthwork sites, geoglyphs, mound sites, and walled enclosures situated in the interfluves of the Purus River in the Brazilian state of Acre and propose a type definition for these sites. The abundant anthropogenic landscape features and their associated material culture indicate considerable human-induced environmental alterations and diverse earthworking traditions that are characteristic of the region of eastern Acre from at least ca. 2000 b.p. onwards.
  • Mesimäki, Marja Helena; Hauru, Kaisa Matilda; Lehvävirta, Susanna (2019)
    Growing and densifying cities set challenges for preserving and enhancing sufficient and good quality green urban environment. Rooftops offer vacant room for additional urban greening that may contribute to the well-being of people and the liveability of cities, but this potential lacks empirical support. In spite of the fact that even small green spaces produce, for example restorative experiences, the literature concerning the experiential and recreational benefits of green roofs is still scarce. To identify the experiential potential of a small urban green roof we explored restorative and other experiences of 178 people visiting a sparsely vegetated green roof in the centre of Helsinki, Finland, using a questionnaire. We showed that the studied green roof provided restorative and other positive experiences to the visitors. The level of perceived restorativeness was relatively high. In addition, the results revealed multiple perceived qualities that reflected visual as well as other sensory experiences, beauty, suitability of the place for oneself and the urban context, nature, desire to explore the place and interestedness, positive excitement, and safety. Furthermore, answers to the open questions revealed a wide range of other observations and feelings, such as peace, joy, excitement and hope. Our study indicates that even a small and rather ascetic accessible green roof has potential to offer a moment of respite in the middle of urban everyday hassle, thus implying that these kinds of solutions may allow for a pinch of beneficial green in places where more diverse and lusher solutions are not possible due to, e.g. the load capacity of a roof
  • Kärnä, Olli-Matti; Heino, Jani; Laamanen, Tiina; Jyrkänkallio-Mikkola, Jenny; Pajunen, Virpi; Soininen, Janne; Tolonen, Kimmo T.; Tukiainen, Helena; Hjort, Jan (2019)
    Context One approach to maintain the resilience of biotic communities is to protect the variability of abiotic characteristics of Earth's surface, i.e. geodiversity. In terrestrial environments, the relationship between geodiversity and biodiversity is well recognized. In streams, the abiotic properties of upstream catchments influence stream communities, but the relationships between catchment geodiversity and aquatic biodiversity have not been previously tested. Objectives The aim was to compare the effects of local environmental and catchment variables on stream biodiversity. We specifically explored the usefulness of catchment geodiversity in explaining the species richness on stream macroinvertebrate, diatom and bacterial communities. Methods We used 3 geodiversity variables, 2 land use variables and 4 local habitat variables to examine species richness variation across 88 stream sites in western Finland. We used boosted regression trees to explore the effects of geodiversity and other variables on biodiversity. Results We detected a clear effect of catchment geodiversity on species richness, although the traditional local habitat and land use variables were the strongest predictors. Especially soil-type richness appeared as an important factor for species richness. While variables related to stream size were the most important for macroinvertebrate richness and partly for bacterial richness, the importance of water chemistry and land use for diatom richness was notable. Conclusions In addition to traditional environmental variables, geodiversity may affect species richness variation in streams, for example through changes in water chemistry. Geodiversity information could be used as a proxy for predicting stream species richness and offers a supplementary tool for conservation efforts.