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.
  • Kangas, Johanna; Ollikainen, Markku (2022)
    Forests can play a significant role both in halting biodiversity loss and in mitigating climate change. A variety of payments for ecosystem services (PES) schemes exists to promote biodiversity conservation in forests. These schemes could be used to strengthen the role of forests as carbon sinks as well. This paper analyzes the implications of supplementing a PES scheme that targets boreal forest biodiversity with a carbon index. We use a site selection framework to examine how the proposed scheme impacts the promotion of both targets. We compare a case where the selection is done solely based on biodiversity values to a case where the selection is done based on both biodiversity and carbon benefits. The carbon index is formulated as current carbon storage or as future carbon sink. Correspondingly, biodiversity is maximized based on either current ecological values or potential ones. We compare equal or differing weights for biodiversity and carbon indexes, and examine trade-offs between biodiversity and CO2 in current and future values. Combined index values increase with the carbon index, but there is a trade-off between biodiversity and CO2 values if the conservation budget is not increased when the carbon index is introduced. There is a temporal trade-off in biodiversity and carbon values between selecting sites based on current or future values. Younger stands are preferred at the expense of old-growth stands with the carbon index. Weights can be used to balance the trade-off between biodiversity and carbon benefits. Overall, risks to losing significant ecological value from the conservation network are negligible, but the limited number of sites decreases the generalizability of the results.
  • 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.
  • Poikolainen, Janne (2022)
    Young people have rarely been studied in the field of second-home research as active subjects, although they play an influential part in contemporary second-home tourism. Based on semi-structured interviews, this study seeks to address the scholarly gap in the existing literature by analysing the experiences of, and attitudes towards, second-home living among 12- to 17-year-old second-home dwellers vacationing in Mantyharju, Finland. The study focuses on the second-home environment as a hybrid space enabling young cottagers to combine elements of a traditionalist lifestyle, outdoor recreation, and late modern technoscape in pursuit of pleasurable and restorative leisure. The findings suggest that young second-home dwellers see outdoor activities and rich natural surroundings, as well as intense familial communality and selected aspects of simple living, as the basis of an enjoyable second-home experience. At the same time, they complement these elements with the active use of mobile and entertainment technology, seeking a satisfying balance between the exotic and the ordinary. The results show that studying young second-home dwellers offers fresh new perspectives not only on second-home tourism and its ongoing changes but also on the leisure preferences of late modern youth in general.
  • 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)
  • Karihtala, Peeter; Porvari, Katja; Roininen, Nelli; Voutilainen, Sari; Mattson, Johanna; Heikkilä, Päivi; Haapasaari, Kirsi-Maria; Selander, Katri (2022)
    The pathophysiology and the optimal treatment of breast neuroendocrine tumours (NETs) are unknown. We compared the mutational profiles of breast NETs (n = 53) with those of 724 publicly available invasive ductal carcinoma (IDC) and 98 pancreatic NET (PNET) cases. The only significantly different pathogenetic or unknown variant rate between breast NETs and IDCs was detected in the TP53 (11.3% in breast NETs and 41% in IDCs, adjusted p value 0.027) and ADCK2 (9.4% in breast NETs vs. 0.28% in IDCs, adjusted p value 0.045) genes. Between breast NETs and PNETs, different pathogenetic or unknown variant frequencies were detected in 30 genes. For example, MEN1 was mutated in only 6% of breast NETs and 37% in PNETs (adjusted p value 0.00050), and GATA3 pathogenetic or unknown variants were only found in 17.0% of breast NETs and 0% in PNETs (adjusted p value 0.0010). The most commonly affected oncogenic pathways in the breast NET cases were PI3K/Akt/mTOR, NOTCH and RTK-RAS pathways. Breast NETs had typically clock-like mutational signatures and signatures associated with defective DNA mismatch repair in their mutational landscape. Our results suggest that the breast NET mutational profile more closely resembles that of IDCs than that of PNETs. These results also revealed several potentially druggable targets, such as MMRd, in breast NETs. In conclusion, breast NETs are indeed a separate breast cancer entity, but their optimal treatment remains to be elucidated.
  • 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.
  • Fernandez-Anez, Nieves; Krasovskiy, Andrey; Muller, Mortimer; Vacik, Harald; Baetens, Jan; Hukic, Emira; Solomun, Marijana Kapovic; Atanassova, Irena; Glushkova, Maria; Bogunovic, Igor; Fajkovic, Hana; Djuma, Hakan; Boustras, George; Adamek, Martin; Devetter, Miloslav; Hrabalikova, Michaela; Huska, Dalibor; Barroso, Petra Martinez; Vaverkova, Magdalena Daria; Zumr, David; Jogiste, Kalev; Metslaid, Marek; Koster, Kajar; Koster, Egle; Pumpanen, Jukka; Ribeiro-Kumara, Caius; Di Prima, Simone; Pastor, Amandine; Rumpel, Cornelia; Seeger, Manuel; Daliakopoulos, Ioannis; Daskalakou, Evangelia; Koutroulis, Aristeidis; Papadopoulou, Maria P.; Stampoulidis, Kosmas; Xanthopoulos, Gavriil; Aszalos, Reka; Balazs, Deak; Kertesz, Miklos; Valko, Orsolya; Finger, David C.; Thorsteinsson, Throstur; Till, Jessica; Bajocco, Sofia; Gelsomino, Antonio; Amodio, Antonio Minervino; Novara, Agata; Salvati, Luca; Telesca, Luciano; Ursino, Nadia; Jansons, Aris; Kitenberga, Mara; Stivrins, Normunds; Brazaitis, Gediminas; Marozas, Vitas; Cojocaru, Olesea; Gumeniuc, Iachim; Sfecla, Victor; Imeson, Anton; Veraverbeke, Sander; Mikalsen, Ragni Fjellgaard; Koda, Eugeniusz; Osinski, Piotr; Meira Castro, Ana C.; Nunes, Joao Pedro; Oom, Duarte; Vieira, Diana; Rusu, Teodor; Bojovic, Srdan; Djordjevic, Dragana; Popovic, Zorica; Protic, Milan; Sakan, Sanja; Glasa, Jan; Kacikova, Danica; Lichner, Lubomir; Majlingova, Andrea; Vido, Jaroslav; Ferk, Mateja; Ticar, Jure; Zorn, Matija; Zupanc, Vesna; Hinojosa, M. Belen; Knicker, Heike; Lucas-Borja, Manuel Esteban; Pausas, Juli; Prat-Guitart, Nuria; Ubeda, Xavier; Vilar, Lara; Destouni, Georgia; Ghajarnia, Navid; Kalantari, Zahra; Seifollahi-Aghmiuni, Samaneh; Dindaroglu, Turgay; Yakupoglu, Tugrul; Smith, Thomas; Doerr, Stefan; Cerda, Artemi (2021)
    Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009-2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action "Fire and the Earth System: Science & Society" funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.