| 1. |
- Abbey-Lee, Robin, et al.
(författare)
-
Adaptive individual variation in phenological responses to perceived predation levels
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The adaptive evolution of timing of breeding (a component of phenology) in response to environmental change requires individual variation in phenotypic plasticity for selection to act upon. A major question is what processes generate this variation. Here we apply multi-year manipulations of perceived predation levels (PPL) in an avian predator-prey system, identifying phenotypic plasticity in phenology as a key component of alternative behavioral strategies with equal fitness payoffs. We show that under low-PPL, faster (versus slower) exploring birds breed late (versus early); the pattern is reversed under high-PPL, with breeding synchrony decreasing in conjunction. Timing of breeding affects reproductive success, yet behavioral types have equal fitness. The existence of alternative behavioral strategies thus explains variation in phenology and plasticity in reproductive behavior, which has implications for evolution in response to anthropogenic change.
|
|
| 2. |
- Acs, B, et al.
(författare)
-
An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5440-
-
Tidskriftsartikel (refereegranskat)abstract
- Assessment of tumor infiltrating lymphocytes (TILs) as a prognostic variable in melanoma has not seen broad adoption due to lack of standardization. Automation could represent a solution. Here, using open source software, we build an algorithm for image-based automated assessment of TILs on hematoxylin-eosin stained sections in melanoma. Using a retrospective collection of 641 melanoma patients comprising four independent cohorts; one training set (N = 227) and three validation cohorts (N = 137, N = 201, N = 76) from 2 institutions, we show that the automated TIL scoring algorithm separates patients into favorable and poor prognosis cohorts, where higher TILs scores were associated with favorable prognosis. In multivariable analyses, automated TIL scores show an independent association with disease-specific overall survival. Therefore, the open source, automated TIL scoring is an independent prognostic marker in melanoma. With further study, we believe that this algorithm could be useful to define a subset of patients that could potentially be spared immunotherapy.
|
|
| 3. |
- Adamczyk, B., et al.
(författare)
-
Plant roots increase both decomposition and stable organic matter formation in boreal forest soil
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Boreal forests are ecosystems with low nitrogen (N) availability that store globally significant amounts of carbon (C), mainly in plant biomass and soil organic matter (SOM). Although crucial for future climate change predictions, the mechanisms controlling boreal C and N pools are not well understood. Here, using a three-year field experiment, we compare SOM decomposition and stabilization in the presence of roots, with exclusion of roots but presence of fungal hyphae and with exclusion of both roots and fungal hyphae. Roots accelerate SOM decomposition compared to the root exclusion treatments, but also promote a different soil N economy with higher concentrations of organic soil N compared to inorganic soil N accompanied with the build-up of stable SOM-N. In contrast, root exclusion leads to an inorganic soil N economy (i.e., high level of inorganic N) with reduced stable SOM-N buildup. Based on our findings, we provide a framework on how plant roots affect SOM decomposition and stabilization.
|
|
| 4. |
- Aguado, J, et al.
(författare)
-
Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson-Gilford Progeria Syndrome
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4990-
-
Tidskriftsartikel (refereegranskat)abstract
- Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo.
|
|
| 5. |
- Agudelo, LZ, et al.
(författare)
-
Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2767-
-
Tidskriftsartikel (refereegranskat)abstract
- The coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, PGC-1α1 enhances the expression of kynurenine aminotransferases (Kats), which convert kynurenine into kynurenic acid. This reduces kynurenine-associated neurotoxicity and generates glutamate as a byproduct. Here, we show that PGC-1α1 elevates aspartate and glutamate levels and increases the expression of glycolysis and malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization and transfer fuel-derived electrons to mitochondrial respiration. This PGC-1α1-dependent mechanism allows trained muscle to use kynurenine metabolism to increase the bioenergetic efficiency of glucose oxidation. Kat inhibition with carbidopa impairs aspartate biosynthesis, mitochondrial respiration, and reduces exercise performance and muscle force in mice. Our findings show that PGC-1α1 activates the MAS in skeletal muscle, supported by kynurenine catabolism, as part of the adaptations to endurance exercise. This crosstalk between kynurenine metabolism and the MAS may have important physiological and clinical implications.
|
|
| 6. |
- Akula, Murali K, et al.
(författare)
-
Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Rho family proteins are prenylated by geranylgeranyltransferase type I (GGTase-I), which normally target proteins to membranes for GTP-loading. However, conditional deletion of GGIase-I in mouse macrophages increases GTP-loading of Rho proteins, leading to enhanced inflammatory responses and severe rheumatoid arthritis. Here we show that heterozygous deletion of the Rho family gene Rac1, but not Rhoa and Cdc42, reverses inflammation and arthritis in GGTase-I-deficient mice. Non-prenylated Rac1 has a high affinity for the adaptor protein Ras GTPase-activating-like protein 1 (Iqgap1), which facilitates both GTP exchange and ubiquitination-mediated degradation of Rac1. Consistently, inactivating lagapl normalizes Rac1 GTP-loading, and reduces inflammation and arthritis in GGTase-I-deficient mice, as well as prevents statins from increasing Rac1 GTP-loading and cytokine production in macrophages. We conclude that blocking prenylation stimulates Rac1 effector interactions and unleashes proinflammatory signaling. Our results thus suggest that prenylation normally restrains innate immune responses by preventing Rac1 effector interactions.
|
|
| 7. |
- Allum, F, et al.
(författare)
-
Dissecting features of epigenetic variants underlying cardiometabolic risk using full-resolution epigenome profiling in regulatory elements
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1209-
-
Tidskriftsartikel (refereegranskat)abstract
- Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up on adipose-specific regulatory regions under (1) genetic and (2) epigenetic (environmental) regulation via integrational studies. Overall, the comprehensive sequencing of regulatory element methylomes reveals a rich landscape of functional variants linked genetically as well as epigenetically to plasma lipid traits.
|
|
| 8. |
- Andersson Ersman, Peter, et al.
(författare)
-
All-printed large-scale integrated circuits based on organic electrochemical transistors
- 2019
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The communication outposts of the emerging Internet of Things are embodied by ordinary items, which desirably include all-printed flexible sensors, actuators, displays and akin organic electronic interface devices in combination with silicon-based digital signal processing and communication technologies. However, hybrid integration of smart electronic labels is partly hampered due to a lack of technology that (de)multiplex signals between silicon chips and printed electronic devices. Here, we report all-printed 4-to-7 decoders and seven-bit shift registers, including over 100 organic electrochemical transistors each, thus minimizing the number of terminals required to drive monolithically integrated all-printed electrochromic displays. These relatively advanced circuits are enabled by a reduction of the transistor footprint, an effort which includes several further developments of materials and screen printing processes. Our findings demonstrate that digital circuits based on organic electrochemical transistors (OECTs) provide a unique bridge between all-printed organic electronics (OEs) and low-cost silicon chip technology for Internet of Things applications. © 2019, The Author(s).
|
|
| 9. |
- Barnes, Michele L., et al.
(författare)
-
Social-ecological alignment and ecological conditions in coral reefs
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Complex social-ecological interactions underpin many environmental problems. To help capture this complexity, we advance an interdisciplinary network modeling framework to identify important relationships between people and nature that can influence environmental conditions. Drawing on comprehensive social and ecological data from five coral reef fishing communities in Kenya; including interviews with 648 fishers, underwater visual census data of reef ecosystem condition, and time-series landings data; we show that positive ecological conditions are associated with 'social-ecological network closure' - i.e., fully linked and thus closed network structures between social actors and ecological resources. Our results suggest that when fishers facing common dilemmas form cooperative communication ties with direct resource competitors, they may achieve positive gains in reef fish biomass and functional richness. Our work provides key empirical insight to a growing body of research on social-ecological alignment, and helps to advance an integrative framework that can be applied empirically in different social-ecological contexts.
|
|
| 10. |
- Barrenäs, Fredrik, et al.
(författare)
-
Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin shows distinct tissue distribution and abundance kinetics in AGMs. Furthermore, AGM monocytes exhibit an embryonic development and repair/regeneration signature featuring TGF-beta and concomitant reduced expression of inflammatory genes compared to RMs. This regenerative wound healing process likely preserves mucosal integrity and prevents inflammatory insults that underlie immune exhaustion in RMs.
|
|
