| 1. |
- Abelein, Axel, et al.
(författare)
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Zinc as chaperone-mimicking agent for retardation of amyloid beta peptide fibril formation
- 2015
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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. ; 112:17, s. 5407-5412
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Tidskriftsartikel (refereegranskat)abstract
- Metal ions have emerged to play a key role in the aggregation process of amyloid beta (A beta) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic A beta-Zn2+ binding features as well as how Zn2+ modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn2+ effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc A beta(40) aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn2+, the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn2+ transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn2+ ion, forming a marginally stable, short-lived folded A beta(40) species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded A beta(40)-Zn2+ complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for A beta(40).
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| 2. |
- Acerbi, Alberto, et al.
(författare)
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Cultural evolution and individual development of openness and conservatism
- 2009
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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. ; 106:45, s. 18931-18935
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Tidskriftsartikel (refereegranskat)abstract
- We present a model of cultural evolution in which an individual's propensity to engage in social learning is affected by social learning itself. We assume that individuals observe cultural traits displayed by others and decide whether to copy them based on their overall preference for the displayed traits. Preferences, too, can be transmitted between individuals. Our results show that such cultural dynamics tends to produce conservative individuals, i.e., individuals who are reluctant to copy new traits. Openness to new information, however, can be maintained when individuals need significant time to acquire the cultural traits that make them effective cultural models. We show that a gradual enculturation of young individuals by many models and a larger cultural repertoire to be acquired are favorable circumstances for the long-term maintenance of openness in individuals and groups. Our results agree with data about lifetime personality change, showing that openness to new information decreases with age. Our results show that cultural remodeling of cultural transmission is a powerful force in cultural evolution, i.e., that cultural evolution can change its own dynamics
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| 3. |
- Ahn, Young O., et al.
(författare)
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Conformational coupling between the active site and residues within the K-C-channel of the Vibrio cholerae cbb(3)-type (C-family) oxygen reductase
- 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. - 0027-8424 .- 1091-6490. ; 111:42, s. E4419-E4428
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory chains of nearly all aerobic organisms are terminated by proton-pumping heme-copper oxygen reductases (HCOs). Previous studies have established that C-family HCOs contain a single channel for uptake from the bacterial cytoplasm of all chemical and pumped protons, and that the entrance of the K-C-channel is a conserved glutamate in subunit III. However, the majority of the K-C-channel is within subunit I, and the pathway from this conserved glutamate to subunit I is not evident. In the present study, molecular dynamics simulations were used to characterize a chain of water molecules leading from the cytoplasmic solution, passing the conserved glutamate in subunit III and extending into subunit I. Formation of the water chain, which controls the delivery of protons to the K-C-channel, was found to depend on the conformation of Y241(Vc), located in subunit I at the interface with subunit III. Mutations of Y241(Vc) (to A/F/H/S) in the Vibrio cholerae cbb(3) eliminate catalytic activity, but also cause perturbations that propagate over a 28-angstrom distance to the active site heme b(3). The data suggest a linkage between residues lining the KC-channel and the active site of the enzyme, possibly mediated by transmembrane helix alpha 7, which contains both Y241(Vc) and the active site crosslinked Y255(Vc), as well as two Cu-B histidine ligands. Other mutations of residues within or near helix alpha 7 also perturb the active site, indicating that this helix is involved in modulation of the active site of the enzyme.
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| 4. |
- Almås, Ingvild, et al.
(författare)
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Global evidence on the selfish rich inequality hypothesis
- 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 .- 1091-6490. ; 119:3
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Tidskriftsartikel (refereegranskat)abstract
- We report on a study of whether people believe that the rich are richer than the poor because they have been more selfish in life, using data from more than 26,000 individuals in 60 countries. The findings show a strong belief in the selfish rich inequality hypothesis at the global level; in the majority of countries, the mode is to strongly agree with it. However, we also identify important between- and within-country variation. We find that the belief in selfish rich inequality is much stronger in countries with extensive corruption and weak institutions and less strong among people who are higher in the income distribution in their society. Finally, we show that the belief in selfish rich inequality is predictive of people’s policy views on inequality and redistribution: It is significantly positively associated with agreeing that inequality in their country is unfair, and it is significantly positively associated with agreeing that the government should aim to reduce inequality. These relationships are highly significant both across and within countries and robust to including country-level or individual-level controls and using Lasso-selected regressors. Thus, the data provide compelling evidence of people believing that the rich are richer because they have been more selfish in life and perceiving selfish behavior as creating unfair inequality and justifying equalizing policies.
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| 5. |
- Alonso-Mori, Roberto, et al.
(författare)
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Energy-dispersive X-ray emission spectroscopy using an X-ray free-electron laser in a shot-by-shot mode
- 2012
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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. ; 109:47, s. 19103-19107
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Tidskriftsartikel (refereegranskat)abstract
- The ultrabright femtosecond X-ray pulses provided by X-ray free-electron lasers open capabilities for studying the structure and dynamics of a wide variety of systems beyond what is possible with synchrotron sources. Recently, this probe-before-destroy approach has been demonstrated for atomic structure determination by serial X-ray diffraction of microcrystals. There has been the question whether a similar approach can be extended to probe the local electronic structure by X-ray spectroscopy. To address this, we have carried out femtosecond X-ray emission spectroscopy (XES) at the Linac Coherent Light Source using redox-active Mn complexes. XES probes the charge and spin states as well as the ligand environment, critical for understanding the functional role of redox-active metal sites. K beta(1,3) XES spectra of Mn-II and Mn-2(III,IV) complexes at room temperature were collected using a wavelength dispersive spectrometer and femtosecond X-ray pulses with an individual dose of up to > 100 MGy. The spectra were found in agreement with undamaged spectra collected at low dose using synchrotron radiation. Our results demonstrate that the intact electronic structure of redox active transition metal compounds in different oxidation states can be characterized with this shot-by-shot method. This opens the door for studying the chemical dynamics of metal catalytic sites by following reactions under functional conditions. The technique can be combined with X-ray diffraction to simultaneously obtain the geometric structure of the overall protein and the local chemistry of active metal sites and is expected to prove valuable for understanding the mechanism of important metalloproteins, such as photosystem II.
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| 6. |
- Altmejd, Adam, et al.
(författare)
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Inequality and COVID-19 in Sweden : Relative risks of nine bad life events, by four social gradients, in pandemic vs. prepandemic years
- 2023
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Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:46
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic struck societies directly and indirectly, not just challenging population health but disrupting many aspects of life. Different effects of the spreading virus—and the measures to fight it—are reported and discussed in different scientific fora, with hard-to-compare methods and metrics from different traditions. While the pandemic struck some groups more than others, it is difficult to assess the comprehensive impact on social inequalities. This paper gauges social inequalities using individual-level administrative data for Sweden’s entire population. We describe and analyze the relative risks for different social groups in four dimensions—gender, education, income, and world region of birth—to experience three types of COVID-19 incidence, as well as six additional negative life outcomes that reflect general health, access to medical care, and economic strain. During the pandemic, the overall population faced severe morbidity and mortality from COVID-19 and saw higher all-cause mortality, income losses and unemployment risks, as well as reduced access to medical care. These burdens fell more heavily on individuals with low income or education and on immigrants. Although these vulnerable groups experienced larger absolute risks of suffering the direct and indirect consequences of the pandemic, the relative risks in pandemic years (2020 and 2021) were conspicuously similar to those in prepandemic years (2016 to 2019).
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| 7. |
- Andersson, Charlotta S, et al.
(författare)
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A Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold
- 2009
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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. ; 106:14, s. 5633-8
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis R2c is the prototype for a recently discovered group of ribonucleotide reductase R2 proteins that use a heterodinuclear Mn/Fe redox cofactor for radical generation and storage. Here, we show that the Mycobacterium tuberculosis protein Rv0233, an R2 homologue and a potential virulence factor, contains the heterodinuclear manganese/iron-carboxylate cofactor but displays a drastic remodeling of the R2 protein scaffold into a ligand-binding oxidase. The first structural characterization of the heterodinuclear cofactor shows that the site is highly specific for manganese and iron in their respective positions despite a symmetric arrangement of coordinating residues. In this protein scaffold, the Mn/Fe cofactor supports potent 2-electron oxidations as revealed by an unprecedented tyrosine-valine crosslink in the active site. This wolf in sheep's clothing defines a distinct functional group among R2 homologues and may represent a structural and functional counterpart of the evolutionary ancestor of R2s and bacterial multicomponent monooxygenases.
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| 8. |
- Antonelli, A, et al.
(författare)
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Tracing the impact of the Andean uplift on Neotropical plant evolution : evidence from the coffee family
- 2009
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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. ; 106:24, s. 9749-9754
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Tidskriftsartikel (refereegranskat)abstract
- Recent phylogenetic studies have revealed the major role played by the uplift of the Andes in the extraordinary diversification of the Neotropical flora. These studies, however, have typically considered the Andean uplift as a single, time-limited event fostering the evolution of highland elements. This contrasts with geological reconstructions indicating that the uplift occurred in discrete periods from west to east and that it affected different regions at different times. We introduce an approach for integrating Andean tectonics with biogeographic reconstructions of Neotropical plants, using the coffee family (Rubiaceae) as a model group. The distribution of this family spans highland and montane habitats as well as tropical lowlands of Central and South America, thus offering a unique opportunity to study the influence of the Andean uplift on the entire Neotropical flora. Our results suggest that the Rubiaceae originated in the Paleotropics and used the boreotropical connection to reach South America. The biogeographic patterns found corroborate the existence of a long-lasting dispersal barrier between the Northern and Central Andes, the "Western Andean Portal.'' The uplift of the Eastern Cordillera ended this barrier, allowing dispersal of boreotropical lineages to the South, but gave rise to a huge wetland system ("Lake Pebas'') in western Amazonia that prevented in situ speciation and floristic dispersal between the Andes and Amazonia for at least 6 million years. Here, we provide evidence of these events in plants
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| 9. |
- Aze, Tracy, et al.
(författare)
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Identifying anagenesis cladogenesis in the fossil record
- 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. - 0027-8424 .- 1091-6490. ; 110:32, s. E2946-E2946
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Bak-Coleman, Joseph B., et al.
(författare)
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Stewardship of global collective behavior
- 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. ; 118:27
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Tidskriftsartikel (refereegranskat)abstract
- Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a crisis discipline just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
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