Water temperature is critical for the ecology of lakes. However, the ability to predict its spatial and seasonal variation is constrained by the lack of a thermal classification system. Here we ...define lake thermal regions using objective analysis of seasonal surface temperature dynamics from satellite observations. Nine lake thermal regions are identified that mapped robustly and largely contiguously globally, even for small lakes. The regions differed from other global patterns, and so provide unique information. Using a lake model forced by 21
century climate projections, we found that 12%, 27% and 66% of lakes will change to a lower latitude thermal region by 2080-2099 for low, medium and high greenhouse gas concentration trajectories (Representative Concentration Pathways 2.6, 6.0 and 8.5) respectively. Under the worst-case scenario, a 79% reduction in the number of lakes in the northernmost thermal region is projected. This thermal region framework can facilitate the global scaling of lake-research.
Lianas are a key component of tropical forests; however, most surveys are too small to accurately quantify liana community composition, diversity, abundance, and spatial distribution - critical ...components for measuring the contribution of lianas to forest processes. In 2007, we tagged, mapped, measured the diameter, and identified all lianas ≥1 cm rooted in a 50-ha plot on Barro Colorado Island, Panama (BCI). We calculated liana density, basal area, and species richness for both independently rooted lianas and all rooted liana stems (genets plus clones). We compared spatial aggregation patterns of liana and tree species, and among liana species that varied in the amount of clonal reproduction. We also tested whether liana and tree densities have increased on BCI compared to surveys conducted 30-years earlier. This study represents the most comprehensive spatially contiguous sampling of lianas ever conducted and, over the 50 ha area, we found 67,447 rooted liana stems comprising 162 species. Rooted lianas composed nearly 25% of the woody stems (trees and lianas), 35% of woody species richness, and 3% of woody basal area. Lianas were spatially aggregated within the 50-ha plot and the liana species with the highest proportion of clonal stems more spatially aggregated than the least clonal species, possibly indicating clonal stem recruitment following canopy disturbance. Over the past 30 years, liana density increased by 75% for stems ≥1 cm diameter and nearly 140% for stems ≥5 cm diameter, while tree density on BCI decreased 11.5%; a finding consistent with other neotropical forests. Our data confirm that lianas contribute substantially to tropical forest stem density and diversity, they have highly clumped distributions that appear to be driven by clonal stem recruitment into treefall gaps, and they are increasing relative to trees, thus indicating that lianas will play a greater role in the future dynamics of BCI and other neotropical forests.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It seems paradoxical to suggest that theories of learning might be used to explain policy failure. Yet the Brexit fiasco connects with recent approaches linking varieties of policy learning to policy ...pathologies. This article sets out to explain the UK government's (mis)management of the Brexit process from June 2016 to May 2019 from a policy learning perspective. Drawing on interviews with UK policy-makers and stakeholders, we ask how did the UK government seek to learn during the Brexit negotiations? We consider four modes of learning: reflexivity, epistemic, hierarchical, and bargaining. By empirically tracing the policy process and scope conditions for each of these, we argue that learning through the first three modes proved highly dysfunctional. This forced the government to rely on bargaining between competing factions, producing a highly political form of learning which stymied the development of a coherent Brexit strategy. We argue that the analysis of Brexit as a policy process - rather than a political event - reveals how policy dynamics play an important role in shaping the political context within which they are located. The article concludes that public policy analysis can, therefore, add significant value to our understanding of Brexit by endogenising accounts of macro political developments.
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BFBNIB, NUK, ODKLJ, PILJ, SAZU, UL, UM, UPUK
The emerging technique of microfluidic digital PCR (dPCR) offers a unique approach to real-time quantitative PCR for measuring nucleic acids that may be particularly suited for low-level detection. ...In this study, we evaluated the quantitative capabilities of dPCR when measuring small amounts (<200 copies) of DNA and investigated parameters influencing technical performance. We used various DNA templates, matrixes, and assays to evaluate the precision, sensitivity and reproducibility of dPCR, and demonstrate that this technique can be highly reproducible when performed at different times and when different primer sets are targeting the same molecule. dPCR exhibited good analytical sensitivity and was reproducible outside the range recommended by the instrument manufacturer; detecting 16 estimated targets with high precision. The inclusion of carrier had no effect on this estimated quantity, but did improve measurement precision. We report disagreement when using dPCR to measure different template types and when comparing the estimated quantities by dPCR and UV spectrophotometry. Finally, we also demonstrate that preamplification can impose a significant measurement bias. These findings provide an independent assessment of low copy molecular measurement using dPCR and underline important factors for consideration in dPCR experimental design.
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IJS, KILJ, NUK, PNG, UL, UM
Plasma levels of HDL cholesterol are inversely associated with CVD progression. It is becoming increasingly clear that HDL plays important roles in immunity that go beyond its traditionally ...understood roles in lipid transport. We previously reported that HDL interaction with regulatory T cells (Treg) protected them from apoptosis, which could be a mechanism underlying the broad anti-inflammatory effect of HDL. Herein, we extend our work to show that HDL interacts mainly with memory Treg, particularly with the highly suppressive effector memory Treg, by limiting caspase-dependent apoptosis in an Akt-dependent manner. Reconstitution experiments identified the protein component of HDL as the primary driver of the effect, though the most abundant HDL protein, apolipoprotein A-I (APOA1), was inactive. In contrast, APOE-depleted HDL failed to rescue effector memory Treg, suggesting the critical role of APOE proteins. HDL particles reconstituted with APOE, and synthetic phospholipids blunted Treg apoptosis at physiological concentrations. The APOE3 and APOE4 isoforms were the most efficient. Similar results were obtained when lipid-free recombinant APOEs were tested. Binding experiments showed that lipid-free APOE3 bound to memory Treg but not to naive Treg. Overall, our results show that APOE interaction with Treg results in blunted caspase-dependent apoptosis and increased survival. As dysregulation of HDL-APOE levels has been reported in CVD and obesity, our data bring new insight on how this defect may contribute to these diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiotherapy (CRT) are incompletely characterized.
We performed integrated ...whole-exome/transcriptome sequencing and immune infiltrate analysis on rectal adenocarcinoma tumors prior to neoadjuvant CRT (pre-CRT) and at time of resection (post-CRT) in 17 patients 8 complete/partial responders, 9 nonresponders (NR).
CRT was not associated with increased tumor mutational burden or neoantigen load and did not alter the distribution of established somatic tumor mutations in rectal cancer. Concurrent
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mutations (KP) associated with NR tumors and were enriched for an epithelial-mesenchymal transition transcriptional program. Furthermore, NR was associated with reduced CD4/CD8 T-cell infiltrates and a post-CRT M2 macrophage phenotype. Absence of any local tumor recurrences, KP/NR status predicted worse progression-free survival, suggesting that local immune escape during or after CRT with specific genomic features contributes to distant progression.
Overall, while CRT did not impact genomic profiles, CRT impacted the tumor immune microenvironment, particularly in resistant cases.
The underlying mechanisms of appendage regeneration remain largely unknown and uncovering these mechanisms in capable organisms has far‐reaching implications for potential treatments in humans. ...Recent studies implicate a requirement for metabolic reprogramming reminiscent of the Warburg effect during successful appendage and organ regeneration. As changes are thus predicted to be highly dynamic, methods permitting direct, real‐time visualisation of metabolites at the tissue and organismal level would offer a significant advance in defining the influence of metabolism on regeneration and healing. We sought to examine whether glycolytic activity was altered during larval fin regeneration, utilising the genetically encoded biosensor, Laconic, enabling the spatiotemporal assessment of lactate levels in living zebrafish. We present evidence for a rapid increase in lactate levels within min following injury, with a role of aerobic glycolysis in actomyosin contraction and wound closure. We also find a second wave of lactate production, associated with overall larval tail regeneration. Chemical inhibition of glycolysis attenuates both the contraction of the wound and regrowth of tissue following tail amputation, suggesting aerobic glycolysis is necessary at two distinct stages of regeneration.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. ...Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy, including radiographic response, across multiple cancer types to examine additional tumor genomic features that contribute to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However, these features were often interrelated, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and multifaceted manner to enhance the ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.
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