90 research outputs found

    Racial disparities in problems with voting

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    Electoral laws in the United States are causing hurdles for participation which affect the racial minority population in greater degree than for the white population. This thesis looks at racial disparities in problems with voting with data from the 2020 Cooperative Election Study. A logistic fixed effect regression model shows the results of racial minorities who are Black, Hispanic, and Two or more races have statistically significant increased odds in having problems with voting, compared to White. When adding the structural variables, some of this is explained by low education, living in urban areas and being younger, controlled for the state the respondent lives in. There are still significant results that Hispanics and Two or more races have increased odds in having problems with voting, compared to White, controlled for education, rurality, age, and state. These laws excludes eligible voters from the American democracy. Voting is a cornerstone in a democracy and should represent the will of all the people. Exclusion of racial minorities violates with the definition of Robert Dahl, that a democracy “is the continuing responsiveness of the government to the preferences of its citizens, considered as political equals” (Dahl 1971, 1). When excluded, racial minorities are not political equals, the government is not being responsive to their preferences, and they don’t possess the opportunity to vote them out. Inclusion should always be desirable as a democratic ideal

    NAA10 p.(D10G) and NAA10 p.(L11R) variants hamper formation of the NatA N-terminal acetyltransferase complex

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    The majority of the human proteome is subjected to N-terminal (Nt) acetylation catalysed by N-terminal acetyltransferases (NATs). The NatA complex is composed of two core subunits—the catalytic subunit NAA10 and the ribosomal anchor NAA15. Furthermore, NAA10 may also have catalytic and non-catalytic roles independent of NatA. Several inherited and de novo NAA10 variants have been associated with genetic disease in humans. In this study, we present a functional analysis of two de novo NAA10 variants, c.29A>G p.(D10G) and c.32T>G p.(L11R), previously identified in a male and a female, respectively. Both of these neighbouring amino acids are highly conserved in NAA10. Immunoprecipitation experiments revealed that both variants hamper complex formation with NAA15 and are thus likely to impair NatA-mediated Nt-acetylation in vivo. Despite their common impact on NatA formation, in vitro Nt-acetylation assays showed that the variants had opposing impacts on NAA10 catalytic activity. While NAA10 c.29A>G p.(D10G) exhibits normal intrinsic NatA activity and reduced monomeric NAA10 NAT activity, NAA10 c.32T>G p.(L11R) displays reduced NatA activity and normal NAA10 NAT activity. This study expands the scope of research into the functional consequences of NAA10 variants and underlines the importance of understanding the diverse cellular roles of NAA10 in disease mechanisms.publishedVersio

    Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK

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    The human N-terminal acetyltransferase E (NatE) contains NAA10 and NAA50 catalytic, and NAA15 auxiliary subunits and associates with HYPK, a protein with intrinsic NAA10 inhibitory activity. NatE co-translationally acetylates the N-terminus of half the proteome to mediate diverse biological processes, including protein half-life, localization, and interaction. The molecular basis for how NatE and HYPK cooperate is unknown. Here, we report the cryo-EM structures of human NatE and NatE/HYPK complexes and associated biochemistry. We reveal that NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. NAA50 and HYPK each contribute to NAA10 activity inhibition through structural alteration of the NAA10 substrate-binding site. NAA50 activity is increased through NAA15 tethering, but is inhibited by HYPK through structural alteration of the NatE substrate-binding site. These studies reveal the molecular basis for coordinated N-terminal acetylation by NatE and HYPK.publishedVersio

    NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy

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    Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.publishedVersio

    NAA10 dysfunction with normal NatA-complex activity in a girl with non-syndromic ID and a de novo NAA10 p.(V111G) variant - a case report

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    Background: The NAA10-NAA15 (NatA) protein complex is an N-terminal acetyltransferase responsible for acetylating ~ 40% of eukaryotic proteins. In recent years, NAA10 variants have been found in patients with an X-linked developmental disorder called Ogden syndrome in its most severe form and, in other familial or de novo cases, with variable degrees of syndromic intellectual disability (ID) affecting both sexes. Case presentation: Here we report and functionally characterize a novel and de novo NAA10 (NM_003491.3) c.332 T > G p.(V111G) missense variant, that was detected by trio-based whole exome sequencing in an 11 year old girl with mild/moderate non-syndromic intellectual disability. She had delayed motor and language development, but normal behavior without autistic traits. Her blood leukocyte X-inactivation pattern was within normal range (80/20). Functional characterization of NAA10-V111G by cycloheximide chase experiments suggests that NAA10-V111G has a reduced stability compared to NAA10-WT, and in vitro acetylation assays revealed a reduced enzymatic activity of monomeric NAA10-V111G but not for NAA10-V111G in complex with NAA15 (NatA enzymatic activity). Conclusions: We show that NAA10-V111G has a reduced stability and monomeric catalytic activity, while NatA function remains unaltered. This is the first example of isolated NAA10 dysfunction in a case of ID, suggesting that the syndromic cases may also require a degree of compromised NatA function.publishedVersio

    Scaling of Entanglement close to a Quantum Phase Transitions

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    In this Letter we discuss the entanglement near a quantum phase transition by analyzing the properties of the concurrence for a class of exactly solvable models in one dimension. We find that entanglement can be classified in the framework of scaling theory. Further, we reveal a profound difference between classical correlations and the non-local quantum correlation, entanglement: the correlation length diverges at the phase transition, whereas entanglement in general remains short ranged.Comment: 4 pages, 4 figures, revtex. Stylistic changes and format modifie

    Detection of multipartite entanglement with two-body correlations

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    We show how to detect entanglement with criteria built from simple two-body correlation terms. Since many natural Hamiltonians are sums of such correlation terms, our ideas can be used to detect entanglement by energy measurement. Our criteria can straightforwardly be applied for detecting different forms of multipartite entanglement in familiar spin models in thermal equilibrium.Comment: 5 pages including 2 figures, LaTeX; for the proceedings of the DPG spring meeting, Berlin, March 200

    Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays

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    We study transition form factors for radiative and rare semi-leptonic B-meson decays into light pseudoscalar or vector mesons, combining theoretical constraints and phenomenological information from Lattice QCD, light-cone sum rules, and dispersive bounds. We pay particular attention to form factor parameterisations which are based on the so-called series expansion, and study the related systematic uncertainties on a quantitative level. In this context, we also provide the NLO corrections to the correlation function between two flavour-changing tensor currents, which enters the unitarity constraints for the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion about relevance of unitarity bounds modified; form factor fits unaffected; references added; v3: discussion on truncation of series expansion added, matches version to be published in JHEP; v4: corrected typos in Tables 5 and

    Entangled Quantum States of Magnetic Dipoles

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    Free magnetic moments usually manifest themselves in Curie Laws, where weak external magnetic fields produce magnetizations diverging as the reciprocal 1/T of the temperature. for a variety of materials that do not disply static magnetism, including doped semiconductors and certain rare earth intermetallics, the 1/T law is changed to a power law T^-a with a<1. We report here that a considerably simpler material, namely an insulating magneticsalt can also display such a power law, and show via comparison to specific heat data and numerical simulations that quantum mechanics is crucial for its formation. Two quantum mechanical phenomena are needed, namely level splitting - which affects the spectrum of excited states - and entanglement - where the wavefunction of a system with several degrees of freedom cannot be written as a product of wavefunctions for each degree of freedom. Entanglement effects become visible for remarkably small tunnelling terms, and are turned on well before tunnelling has visible effects on the spectrum. Our work is significant because it illustrates that entanglement is at the very heart of a very simple experimental observation for an insulating quantum spin system.Comment: 17 pages, 4 figure

    Twenty-Two Years of Warming, Fertilisation and Shading of Subarctic Heath Shrubs Promote Secondary Growth and Plasticity but Not Primary Growth

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    Most manipulation experiments simulating global change in tundra were short-term or did not measure plant growth directly. Here, we assessed the growth of three shrubs (Cassiope tetragona, Empetrum hermaphroditum and Betula nana) at a subarctic heath in Abisko (Northern Sweden) after 22 years of warming (passive greenhouses), fertilisation (nutrients addition) and shading (hessian fabric), and compare this to observations from the first decade of treatment. We assessed the growth rate of current-year leaves and apical stem (primary growth) and cambial growth (secondary growth), and integrated growth rates with morphological measurements and species coverage. Primary- and total growth of Cassiope and Empetrum were unaffected by manipulations, whereas growth was substantially reduced under fertilisation and shading (but not warming) for Betula. Overall, shrub height and length tended to increase under fertilisation and warming, whereas branching increased mostly in shaded Cassiope. Morphological changes were coupled to increased secondary growth under fertilisation. The species coverage showed a remarkable increase in graminoids in fertilised plots. Shrub response to fertilisation was positive in the short-term but changed over time, likely because of an increased competition with graminoids. More erected postures and large, canopies (requiring enhanced secondary growth for stem reinforcement) likely compensated for the increased light competition in Empetrum and Cassiope but did not avoid growth reduction in the shade intolerant Betula. The impact of warming and shading on shrub growth was more conservative. The lack of growth enhancement under warming suggests the absence of long-term acclimation for processes limiting biomass production. The lack of negative effects of shading on Cassiope was linked to morphological changes increasing the photosynthetic surface. Overall, tundra shrubs showed developmental plasticity over the longer term. However, such plasticity was associated clearly with growth rate trends only in fertilised plots
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