The facial width-to-height ratio (FWHR) is the width of the face divided by the height of the upper face. There is mixed evidence for the hypothesis that the FWHR is a cue of threat and dominance in ...the human face. We conducted a systematic review and meta-analyses of all peer-reviewed studies (and 2 unpublished studies) to estimate the magnitude of the sex difference in the FWHR, and the magnitude of the relationship between the FWHR and threatening and dominant behaviours and perceptions. Studies were eligible for inclusion if the authors reported an analysis involving the FWHR. Our analyses revealed that the FWHR was larger in men than in women (d = .11, n = 10,853), cued judgements of masculinity in men (r = .35, n of faces = 487; n of observers = 339), and was related to body mass index (r = .31, n = 2,506). Further, the FWHR predicted both threat behaviour in men (r = .16, n = 4,603) and dominance behaviour in both sexes (r = .12, n = 948) across a variety of indices. Individuals with larger FWHRs were judged by observers as more threatening (r = .46, n of faces = 1,691; n of observers = 2,076) and more dominant (r = .20, n of faces = 603; n of observers = 236) than those with smaller FWHRs. Individuals with larger FWHRs were also judged as less attractive (r = -.26, n of faces = 721; n of observers = 335), especially when women made the judgements. These findings provide some support for the hypothesis that the FWHR is part of an evolved cueing system of intra-sexual threat and dominance in men. A limitation of the meta-analyses on perceptions of threat and dominance were the low number of stimuli involving female and older adult faces.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The synthesis of complex organic molecules requires several stages, from ideation to execution, that require time and effort investment from expert chemists. Here, we report a step toward a paradigm ...of chemical synthesis that relieves chemists from routine tasks, combining artificial intelligence-driven synthesis planning and a robotically controlled experimental platform. Synthetic routes are proposed through generalization of millions of published chemical reactions and validated in silico to maximize their likelihood of success. Additional implementation details are determined by expert chemists and recorded in reusable recipe files, which are executed by a modular continuous-flow platform that is automatically reconfigured by a robotic arm to set up the required unit operations and carry out the reaction. This strategy for computer-augmented chemical synthesis is demonstrated for 15 drug or drug-like substances.
Changes in tree physiology driven by environmental change can alter the balance of forest ecosystem carbon and water fluxes. We performed a meta-analysis of published tree ring literature, comprising ...36 different species across 84 sites globally, to show stimulated leaf photosynthesis, not reduced stomatal conductance, is primarily responsible for recently increasing tree intrinsic water use efficiency (iWUE), which integrates the balance between carbon and water fluxes. Furthermore, we show trends in tree iWUE are similar in magnitude to the increase in atmospheric CO
2
over the 20th century and that climate interacts with CO
2
to modulate tree iWUE. These findings will help to guide efforts of refining the role of forests in process-based models under future environmental change.
We conducted a meta-analysis of carbon and oxygen isotopes from tree ring chronologies representing 34 species across 10 biomes to better understand the environmental drivers and physiological mechanisms leading to historical changes in tree intrinsic water use efficiency (iWUE), or the ratio of net photosynthesis (
A
net
) to stomatal conductance (
g
s
), over the last century. We show a ∼40% increase in tree iWUE globally since 1901, coinciding with a ∼34% increase in atmospheric CO
2
(C
a
), although mean iWUE, and the rates of increase, varied across biomes and leaf and wood functional types. While C
a
was a dominant environmental driver of iWUE, the effects of increasing C
a
were modulated either positively or negatively by climate, including vapor pressure deficit (VPD), temperature, and precipitation, and by leaf and wood functional types. A dual carbon–oxygen isotope approach revealed that increases in
A
net
dominated the observed increased iWUE in ∼83% of examined cases, supporting recent reports of global increases in
A
net
, whereas reductions in
g
s
occurred in the remaining ∼17%. This meta-analysis provides a strong process-based framework for predicting changes in tree carbon gain and water loss across biomes and across wood and leaf functional types, and the interactions between C
a
and other environmental factors have important implications for the coupled carbon–hydrologic cycles under future climate. Our results furthermore challenge the idea of widespread reductions in
g
s
as the major driver of increasing tree iWUE and will better inform Earth system models regarding the role of trees in the global carbon and water cycles.
Clinical studies of non-communicable diseases identify multimorbidities that suggest a common set of predisposing factors. Despite the fact that humans have ~24,000 genes, we do not understand the ...genetic pathways that contribute to the development of multimorbid non-communicable disease. Here we create a multimorbidity atlas of traits based on pleiotropy of spatially regulated genes. Using chromatin interaction and expression Quantitative Trait Loci (eQTL) data, we analyse 20,782 variants (p < 5 × 10
) associated with 1351 phenotypes to identify 16,248 putative spatial eQTL-eGene pairs that are involved in 76,013 short- and long-range regulatory interactions (FDR < 0.05) in different human tissues. Convex biclustering of spatial eGenes that are shared among phenotypes identifies complex interrelationships between nominally different phenotype-associated SNPs. Our approach enables the simultaneous elucidation of variant interactions with target genes that are drivers of multimorbidity, and those that contribute to unique phenotype associated characteristics.
N
-acetylcytidine (ac
C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA
. However, the distribution, ...dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac
C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac
C at single-nucleotide resolution. In human and yeast mRNAs, ac
C sites are not detected but can be induced-at a conserved sequence motif-via the ectopic overexpression of eukaryotic acetyltransferase complexes. By contrast, cross-evolutionary profiling revealed unprecedented levels of ac
C across hundreds of residues in rRNA, tRNA, non-coding RNA and mRNA from hyperthermophilic archaea. Ac
C is markedly induced in response to increases in temperature, and acetyltransferase-deficient archaeal strains exhibit temperature-dependent growth defects. Visualization of wild-type and acetyltransferase-deficient archaeal ribosomes by cryo-electron microscopy provided structural insights into the temperature-dependent distribution of ac
C and its potential thermoadaptive role. Our studies quantitatively define the ac
C landscape, providing a technical and conceptual foundation for elucidating the role of this modification in biology and disease
.
Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting event in human gene control. A small number of regulatory factors influence transcription ...elongation on a global scale. Prior research using small-molecule BET bromodomain inhibitors, such as JQ1, linked BRD4 to context-specific elongation at a limited number of genes associated with massive enhancer regions. Here, the mechanistic characterization of an optimized chemical degrader of BET bromodomain proteins, dBET6, led to the unexpected identification of BET proteins as master regulators of global transcription elongation. In contrast to the selective effect of bromodomain inhibition on transcription, BET degradation prompts a collapse of global elongation that phenocopies CDK9 inhibition. Notably, BRD4 loss does not directly affect CDK9 localization. These studies, performed in translational models of T cell leukemia, establish a mechanism-based rationale for the development of BET bromodomain degradation as cancer therapy.
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•Competitive BET bromodomain inhibition differs from BET protein degradation•BET proteins are master regulators of productive transcription elongation•BET protein degradation is inconsequential for CDK9 recruitment•BET degradation provokes an assembly defect of a transcription elongation complex
Winter et al. delineate fundamental differences in the molecular pharmacology of BET bromodomain inhibition and BET protein degradation. Comparative studies led to the identification of BET proteins as master regulators of transcription elongation. Acute BET protein degradation prompts a global collapse of productive elongation that is independent of CDK9 recruitment.
Proposals for novel spin-orbitronic logic1 and memory devices2 are often predicated on assumptions as to how materials with large spin-orbit coupling interact with ferromagnets when in contact. Such ...interactions give rise to a host of novel phenomena, such as spin-orbit torques3, 4, chiral spin structures5, 6 and chiral spin torques7, 8. These chiral properties are related to the antisymmetric exchange, also referred to as the interfacial Dzyaloshinskii-Moriya interaction (DMI; refs 9, 10). For numerous phenomena, the relative strengths of the symmetric Heisenberg exchange and the DMI are of great importance. Here, we use optical spin-wave spectroscopy (Brillouin light scattering) to directly determine the volume-averaged DMI vector D for a series of Ni80Fe20/Pt thin films, and then compare the nearest-neighbour DMI coupling energy with an independently measured value of the Heisenberg exchange for each sample. We show that the dependence on Ni80Fe20 thickness of both the microscopic symmetric and antisymmetric exchange are nearly identical, consistent with the notion that the fundamentals of the DMI and Heisenberg exchange essentially share the same underlying physics, albeit with different symmetries, as was originally proposed by Moriya11 for superexchange in magnetic oxides, and by Fert and Levy12 for RKKY coupling in metallic spin glasses. Indeed, our result demonstrates the generality of the original DMI theory, insofar as the proportionality of the symmetric and antisymmetric exchange is robust with regard to the details of spin coupling for the material system in question. Although of significant fundamental importance, this result also leads us to a deeper understanding of DMI and how it could be optimized for spin-orbitronic applications.
Strain-release amination Gianatassio, Ryan; Lopchuk, Justin M.; Wang, Jie ...
Science,
01/2016, Letnik:
351, Številka:
6270
Journal Article
Recenzirano
Odprti dostop
To optimize drug candidates, modern medicinal chemists are increasingly turning to an unconventional structural motif: small, strained ring systems. However, the difficulty of introducing ...substituents such as bicyclo1.1.1pentanes, azetidines, or cyclobutanes often outweighs the challenge of synthesizing the parent scaffold itself. Thus, there is an urgent need for general methods to rapidly and directly append such groups onto core scaffolds. Here we report a general strategy to harness the embedded potential energy of effectively spring-loaded C–C and C–N bonds with the most oft-encountered nucleophiles in pharmaceutical chemistry, amines. Strain-release amination can diversify a range of substrates with a multitude of desirable bioisosteres at both the early and late stages of a synthesis. The technique has also been applied to peptide labeling and bioconjugation.
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