| 1711. |
- Ribeiro, Diana, 1987, et al.
(författare)
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Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:42, s. 11127-11132
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are small vesicles released by cells to aid cell-cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found in pancreatic islets of patients with type 2 diabetes (T2D). IAPP is secreted in conjunction with insulin from pancreatic beta cells to regulate glucose metabolism. Here, using a combination of analytical and biophysical methods in vitro, we tested whether EVs isolated from pancreatic islets of healthy patients and patients with T2D modulate IAPP amyloid formation. We discovered that pancreatic EVs from healthy patients reduce IAPP amyloid formation by peptide scavenging, but T2D pancreatic and human serum EVs have no effect. In accordance with these differential effects, the insulin: C-peptide ratio and lipid composition differ between EVs from healthy pancreas and EVs from T2D pancreas and serum. It appears that healthy pancreatic EVs limit IAPP amyloid formation via direct binding as a tissue-specific control mechanism.
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| 1712. |
- Rice, William, et al.
(författare)
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Inter-locus antagonistic coevolution as an engine of speciation : assessment with hemiclonal analysis
- 2005
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:Suppl. 1, s. 6527-6534
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Tidskriftsartikel (refereegranskat)abstract
- One of Ernst Mayr's legacies is the consensus that the allopatry model is the predominant mode of speciation in most sexually reproducing lineages. In this model, reproductive isolation develops as a pleiotropic byproduct of the genetic divergence that develops among physically isolated populations. Presently, there is no consensus concerning which, if any, evolutionary process is primarily responsible for driving the specific genetic divergence that leads to reproductive isolation. Here, we focus on the hypothesis that inter-locus antagonistic coevolution drives rapid genetic divergence among allopatric populations and thereby acts as an important “engine” of speciation. We assert that only data from studies of experimental evolution, rather than descriptive patterns of molecular evolution, can provide definitive evidence for this hypothesis. We describe and use an experimental approach, called hemiclonal analysis, that can be used in theDrosophila melanogaster laboratory model system to simultaneously screen nearly the entire genome for both standing genetic variation within a population and the net-selection gradient acting on the variation. Hemiclonal analysis has four stages: (i) creation of a laboratory “island population”; (ii) cytogenetic cloning of nearly genome-wide haplotypes to construct hemiclones; (iii) measurement of additive genetic variation among hemiclones; and (iv) measurement of the selection gradient acting on phenotypic variation among hemiclones. We apply hemiclonal analysis to test the hypothesis that there is ongoing antagonistic coevolution between the sexes in the D. melanogaster laboratory model system and then discuss the relevance of this analysis to natural systems.
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| 1713. |
- Richtman Feuerborn, Tatiana, et al.
(författare)
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Modern Siberian dog ancestry was shaped by several thousand years of Eurasian-wide trade and human dispersal
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:39
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Tidskriftsartikel (refereegranskat)abstract
- Dogs have been essential to life in the Siberian Arctic for over 9,500 y, and this tight link between people and dogs continues in Siberian communities. Although Arctic Siberian groups such as the Nenets received limited gene flow from neighboring groups, archaeological evidence suggests that metallurgy and new subsistence strategies emerged in Northwest Siberia around 2,000 y ago. It is unclear if the Siberian Arctic dog population was as continuous as the people of the region or if instead admixture occurred, possibly in relation to the influx of material culture from other parts of Eurasia. To address this question, we sequenced and analyzed the genomes of 20 ancient and historical Siberian and Eurasian Steppe dogs. Our analyses indicate that while Siberian dogs were genetically homogenous between 9,500 to 7,000 y ago, later introduction of dogs from the Eurasian Steppe and Europe led to substantial admixture. This is clearly the case in the Iamal-Nenets region (Northwestern Siberia) where dogs from the Iron Age period (∼2,000 y ago) possess substantially less ancestry related to European and Steppe dogs than dogs from the medieval period (∼1,000 y ago). Combined with findings of nonlocal materials recovered from these archaeological sites, including glass beads and metal items, these results indicate that Northwest Siberian communities were connected to a larger trade network through which they acquired genetically distinctive dogs from other regions. These exchanges were part of a series of major societal changes, including the rise of large-scale reindeer pastoralism ∼800 y ago.
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| 1714. |
- Rieckmann, Anna, et al.
(författare)
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Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging
- 2018
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Ingår i: Proceedings of the National Academy of Sciences. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:40, s. 10160-10165
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Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in striatel function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65-86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years). Analyses showed that cortical-caudate functional connectivity was less differentiated in older compared with younger adults (n = 63, age 18-32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less "decoupling" of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical-caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.
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| 1715. |
- Riesbeck, K., et al.
(författare)
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Fluorinated 4-quinolones induce hyperproduction of interleukin 2
- 1989
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 86:8, s. 2809-2813
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Tidskriftsartikel (refereegranskat)abstract
- The fluorinated 4-quinolones are a 'new' group of antibiotics with a broad antibacterial spectrum. They are already widely used in clinical practice. Previous studies have shown that these drugs increase the uptake of [3H]-thymidine into DNA of mitogen-stimulated lymphocytes but inhibit cell growth and immunoglobulin secretion. This study shows that the 4-quinolones strongly (up to 100 times) increase the recovery of interleukin 2 (IL-2) in culture supernatants of phytohemagglutinin (PHA)-stimulated normal human lymphocytes and also prolong the kinetics of IL-2 production. The effect was significant at clinically achievable concentrations (5 μg/ml). In addition to hyperproduction of IL-2, the level of RNA hybridizing with a human IL-2 cDNA probe was also intensely elevated (16-32 times) in PHA-stimulated lymphocytes cultured with ciprofloxacin (80 μg/ml). The mechanism responsible for 4-quinolone-mediated effects on T cells is at present unclear, but evidence is presented that suggests the effect is not exerted at the level of protein kinase C activation. Ciprofloxacin at 80 μg/ml also decreased the expression of IL-2 receptors measured by immunofluorescence with CD 25 antibodies and a radiolabeled IL-2 binding assay. At the same concentration of ciprofloxacin, there was a very low expression of the transferrin receptor and the cell size increased very little in human lymphocytes after PHA stimulation. The enhanced IL-2 production by 4-quinolones may contribute to side effects reported when these drugs are used for treatment of patients.
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| 1716. |
- Rietveld, CA, et al.
(författare)
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Common genetic variants associated with cognitive performance identified using the proxy-phenotype method
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:38, s. 13790-13794
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Tidskriftsartikel (refereegranskat)abstract
- We identify several common genetic variants associated with cognitive performance using a two-stage approach: we conduct a genome-wide association study of educational attainment to generate a set of candidates, and then we estimate the association of these variants with cognitive performance. In older Americans, we find that these variants are jointly associated with cognitive health. Bioinformatics analyses implicate a set of genes that is associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. In addition to the substantive contribution, this work also serves to show a proxy-phenotype approach to discovering common genetic variants that is likely to be useful for many phenotypes of interest to social scientists (such as personality traits).
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| 1717. |
- Rietveld, CA, et al.
(författare)
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Molecular genetics and subjective well-being
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:24, s. 9692-9697
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Tidskriftsartikel (refereegranskat)abstract
- Subjective well-being (SWB) is a major topic of research across the social sciences. Twin and family studies have found that genetic factors may account for as much as 30–40% of the variance in SWB. Here, we study genetic contributions to SWB in a pooled sample of ≈11,500 unrelated, comprehensively-genotyped Swedish and Dutch individuals. We apply a recently developed method to estimate “common narrow heritability”: the fraction of variance in SWB that can be explained by the cumulative additive effects of genetic polymorphisms that are common in the population. Our estimates are 5–10% for single-question survey measures of SWB, and 12–18% after correction for measurement error in the SWB measures. Our results suggest guarded optimism about the prospects of using genetic data in SWB research because, although the common narrow heritability is not large, the polymorphisms that contribute to it could feasibly be discovered with a sufficiently large sample of individuals.
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| 1718. |
- Rincon-Cortes, Millie, et al.
(författare)
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Enduring good memories of infant trauma: Rescue of adult neurobehavioral deficits via amygdala serotonin and corticosterone interaction
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:3, s. 881-886
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Tidskriftsartikel (refereegranskat)abstract
- Children form a strong attachment to their caregiver-even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues-a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.
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| 1719. |
- Ringlander, Johan, et al.
(författare)
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Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 119:6
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Tidskriftsartikel (refereegranskat)abstract
- Adenosine deaminases acting on RNA (ADAR) are RNA-editing enzymes that may restrict viral infection. We have utilized deep sequencing to determine adenosine to guanine (AfiG) mutations, signifying ADAR activity, in clinical samples retrieved from 93 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- infected patients in the early phase of the COVID-19 pandemic. AfiG mutations were detected in 0.035% (median) of RNA residues and were predominantly nonsynonymous. These mutations were rarely detected in the major viral population but were abundant in minor viral populations in which AfiG was more prevalent than any other mutation (P < 0.001). The AfiG substitutions accumulated in the spike protein gene at positions corresponding to amino acids 505 to 510 in the receptor binding motif and at amino acids 650 to 655. The frequency of AfiG mutations in minor viral populations was significantly associated with low viral load (P < 0.001). We additionally analyzed AfiG mutations in 288,247 SARSCoV- 2 major (consensus) sequences representing the dominant viral population. The AfiG mutations observed in minor viral populations in the initial patient cohort were increasingly detected in European consensus sequences between March and June 2020 (P < 0.001) followed by a decline of these mutations in autumn and early winter (P < 0.001). We propose that ADAR-induced deamination of RNA is a significant source of mutated SARS-CoV-2 and hypothesize that the degree of RNA deamination may determine or reflect viral fitness and infectivity. © 2022 National Academy of Sciences. All rights reserved.
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| 1720. |
- Rinnan, Riikka, et al.
(författare)
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Separating direct and indirect effects of rising temperatures on biogenic volatile emissions in the Arctic
- 2020
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 117:51, s. 32476-32483
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Tidskriftsartikel (refereegranskat)abstract
- Plants release to the atmosphere reactive gases, so-called volatile organic compounds (VOCs). The release of VOCs from vegetation is temperature-dependent and controlled by vegetation composition because different plant species release a distinct blend of VOCs. We used modelling approaches on ecosystem VOC release data collected across the Arctic, which is experiencing both rapid warming and vegetation changes. We show that warming strongly stimulates release of plant-derived VOCs and that vegetation changes also increase VOC release, albeit less than temperature directly, and with large geographic differences in the Pan-Arctic area. The increasing VOC flux from the Arctic tundra to the atmosphere may have implications via climate feedbacks, for example, through particle and cloud formation in these regions with low anthropogenic influence.Volatile organic compounds (VOCs) are released from biogenic sources in a temperature-dependent manner. Consequently, Arctic ecosystems are expected to greatly increase their VOC emissions with ongoing climate warming, which is proceeding at twice the rate of global temperature rise. Here, we show that ongoing warming has strong, increasing effects on Arctic VOC emissions. Using a combination of statistical modeling on data from several warming experiments in the Arctic tundra and dynamic ecosystem modeling, we separate the impacts of temperature and soil moisture into direct effects and indirect effects through vegetation composition and biomass alterations. The indirect effects of warming on VOC emissions were significant but smaller than the direct effects, during the 14-y model simulation period. Furthermore, vegetation changes also cause shifts in the chemical speciation of emissions. Both direct and indirect effects result in large geographic differences in VOC emission responses in the warming Arctic, depending on the local vegetation cover and the climate dynamics. Our results outline complex links between local climate, vegetation, and ecosystem–atmosphere interactions, with likely local-to-regional impacts on the atmospheric composition.All data and R scripts used in this manuscript are publicly available and deposited in the Dryad Digital Repository (https://doi.org/10.5061/dryad.kh189323t) (71).
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