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Abstract Background One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker. Materials and Methods We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI cancers. We compared the clinical outcomes of patients with GI cancer harboring MTAP-loss and MTAP-intact tumors in a retrospective study. Results The prevalence of MTAP-loss in GI cancers is 8.30%. MTAP-loss was most prevalent in pancreatic ductal adenocarcinoma (PDAC) at 21.7% and least in colorectal carcinoma (CRC) at 1.1%. MTAP-loss tumors were more prevalent in East Asian patients with PDAC (4.4% vs 3.2%, P = .005) or intrahepatic cholangiocarcinoma (IHCC; 6.4% vs 4.3%, P = .036). Significant differences in the prevalence of potentially targetable genomic alterations (ATM, BRAF, BRCA2, ERBB2, IDH1, PIK3CA, and PTEN) were observed in MTAP-loss tumors and varied according to tumor type. MTAP-loss PDAC, IHCC, and CRC had a lower prevalence of microsatellite instability or elevated tumor mutational burden. Positive PD-L1 tumor cell expression was less frequent among MTAP-loss versus MTAP-intact IHCC tumors (23.2% vs 31.2%, P = .017). Conclusion In GI cancers, MTAP-loss occurs as part of 9p21 loss and has an overall prevalence of 8%. MTAP-loss occurs in 22% of PDAC, 15% of IHCC, 8.7% of gastroesophageal adenocarcinoma, 2.4% of hepatocellular carcinoma, and 1.1% of CRC and is not mutually exclusive with other targetable mutations. Methylthioadenosine phosphorylase (MTAP)-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. This study investigated the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal tumors and its role as a prognostic biomarker.

As the colder regions of the planet warm, species are moving northward and upward from the boreal forest to the tundra biome, a process that has been referred to as borealization. Here, we examine the diverse uses of the term borealization and propose the concept of ‘tundra borealization’ for terrestrial environments to specifically describe shifts and increases in abundance of boreal species into the tundra. We summarize the evidence to date for borealization of plant and animal communities in tundra ecosystems and the different approaches that can be used to quantify borealization. We discuss how land-use change is interacting with climate change, leading to species and community reorganization in colder biomes, and the consequences of borealization for food webs, ecosystem functions and northern livelihoods. Our review brings together the different definitions and lines of evidence for tundra borealization in terrestrial ecosystems to emphasize this important ecological process and rapidly evolving area of research.

Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non‐resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum‐Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non‐resinous). We measured circum‐Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non‐resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti‐herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non‐resinous taxa. This indicates a biome‐wide trade‐off between triterpene‐ or tannin‐dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non‐resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti‐herbivore defence. We conclude that circum‐Arctic variation in birch anti‐herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.

Chronic, low intensity herbivory by invertebrates, termed background herbivory, has been understudied in tundra, yet its impacts are likely to increase in a warmer Arctic. The magnitude of these changes is however hard to predict as we know little about the drivers of current levels of invertebrate herbivory in tundra. We assessed the intensity of invertebrate herbivory on a common tundra plant, the dwarf birch ( Betula glandulosa - nana complex), and investigated its relationship to latitude and climate across the tundra biome. Leaf damage by defoliating, mining and gall-forming invertebrates was measured in samples collected from 192 sites at 56 locations. Our results indicate that invertebrate herbivory is nearly ubiquitous across the tundra biome but occurs at low intensity. On average, invertebrates damaged 11.2% of the leaves and removed 1.4% of total leaf area. The damage was mainly caused by external leaf feeders, and most damaged leaves were only slightly affected (12% leaf area lost). Foliar damage was consistently positively correlated with mid-summer (July) temperature and, to a lesser extent, precipitation in the year of data collection, irrespective of latitude. Our models predict that, on average, foliar losses to invertebrates on dwarf birch are likely to increase by 6–7% over the current levels with a 1 °C increase in summer temperatures. Our results show that invertebrate herbivory on dwarf birch is small in magnitude but given its prevalence and dependence on climatic variables, background invertebrate herbivory should be included in predictions of climate change impacts on tundra ecosystems.

Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence. We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.rotected area networks help species respond to climate warming. However, the contribution of a site’s environmental and conservation-relevant characteristics to these responsesis not well understood. We investigated how composition of nonbreeding waterbird communities (97 species) in the European Union Natura 2000 (N2K) network (3018 sites)changed in response to increases in temperature over 25 years in 26 European countries.We measured community reshuffling based on abundance time series collected under theInternational Waterbird Census relative to N2K sites’ conservation targets, funding, designation period, and management plan status. Waterbird community composition in sitesexplicitly designated to protect them and with management plans changed more quickly inresponse to climate warming than in other N2K sites. Temporal community changes werenot affected by the designation period despite greater exposure to temperature increaseinside late-designated N2K sites. Sites funded under the LIFE program had lower climate-driven community changes than sites that did not received LIFE funding. Our findingsimply that efficient conservation policy that helps waterbird communities respond to cli-mate warming is associated with sites specifically managed for waterbirds. climate adaptation, colonization, conservation policy, distribution change, EU Birds Directive, LIFE program,wetland. Arctic, Betula, birch, herbivory, metabolomics, plant chemical defence, shrubs, tundra

Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence. We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.

Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence. We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.rotected area networks help species respond to climate warming. However, the contribution of a site’s environmental and conservation-relevant characteristics to these responsesis not well understood. We investigated how composition of nonbreeding waterbird communities (97 species) in the European Union Natura 2000 (N2K) network (3018 sites)changed in response to increases in temperature over 25 years in 26 European countries.We measured community reshuffling based on abundance time series collected under theInternational Waterbird Census relative to N2K sites’ conservation targets, funding, designation period, and management plan status. Waterbird community composition in sitesexplicitly designated to protect them and with management plans changed more quickly inresponse to climate warming than in other N2K sites. Temporal community changes werenot affected by the designation period despite greater exposure to temperature increaseinside late-designated N2K sites. Sites funded under the LIFE program had lower climate-driven community changes than sites that did not received LIFE funding. Our findingsimply that efficient conservation policy that helps waterbird communities respond to cli-mate warming is associated with sites specifically managed for waterbirds. climate adaptation, colonization, conservation policy, distribution change, EU Birds Directive, LIFE program,wetland. Arctic, Betula, birch, herbivory, metabolomics, plant chemical defence, shrubs, tundra

The above mentioned article was originally scheduled for publication in the special issue on Ecology of Tundra Arthropods with guest editors Toke T. Høye . Lauren E. Culler. Erroneously, the article was published in Polar Biology, Volume 40, Issue 11, November, 2017. The publisher sincerely apologizes to the guest editors and the authors for the inconvenience caused.

Double-stranded (ds)RNA viruses replicate and transcribe their genome within a proteinaceous viral capsid to evade host cell defenses. While s members use conservative transcription, most dsRNA viruses, including cystoviruses, utilize semi-conservative transcription, where the positive strand of the genome functions as mRNA. Here, we visualize semi-conservative transcription activation in cystovirus ɸ6 double-layered particles using cryogenic electron microscopy. We observe nucleotide-triggered disassembly of the domain-swapped outer capsid layer, subsequent expansion of the inner capsid layer, and stepwise assembly of transcription complexes at the opposing poles of the spooled dsRNA genome. These complexes consist of the viral polymerases embedded into a triskelion formed by the minor protein P7, which we show as essential for continuous transcription. The packaging hexamers proximal to the transcription sites channel the viral mRNA exit. Our results define the complex molecular pathway from the quiescent state to activated semi-conservative transcription.