Heritable variation in gene expression is common within and between species. This variation arises from mutations that alter the form or function of molecular gene regulatory networks that are then ...filtered by natural selection. High-throughput methods for introducing mutations and characterizing their cis- and trans-regulatory effects on gene expression (particularly, transcription) are revealing how different molecular mechanisms generate regulatory variation, and studies comparing these mutational effects with variation seen in the wild are teasing apart the role of neutral and non-neutral evolutionary processes. This integration of molecular and evolutionary biology allows us to understand how the variation in gene expression we see today came to be and to predict how it is most likely to evolve in the future.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
We have identified excited exciton states in monolayers of MoS2 and WS2 supported on fused silica by means of photoluminescence excitation spectroscopy. In monolayer WS2, the positions of the excited ...A exciton states imply an exciton binding energy of 0.32 eV. In monolayer MoS2, excited exciton transitions are observed at energies of 2.24 and 2.34 eV. Assigning these states to the B exciton Rydberg series yields an exciton binding energy of 0.44 eV.
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IJS, KILJ, NUK, PNG, UL, UM
The evolution of sexual dimorphism is constrained by a shared genome, leading to 'sexual antagonism', in which different alleles at given loci are favoured by selection in males and females. Despite ...its wide taxonomic incidence, we know little about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we propose that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We have experimentally determined the energies of the ground and first four excited excitonic states of the fundamental optical transition in monolayer WS2, a model system for the growing class of ...atomically thin two-dimensional semiconductor crystals. From the spectra, we establish a large exciton binding energy of 0.32 eV and a pronounced deviation from the usual hydrogenic Rydberg series of energy levels of the excitonic states. We explain both of these results using a microscopic theory in which the nonlocal nature of the effective dielectric screening modifies the functional form of the Coulomb interaction. These strong but unconventional electron-hole interactions are expected to be ubiquitous in atomically thin materials.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
•Queensland has introduced a hazard perception test as part of the licensing process.•Drivers who failed the test were 25% more likely to crash within the following year.•Drivers who failed were also ...17% more likely to have crashed prior to the test.•These significant results support the validity of the hazard perception test.
In 2008, the state of Queensland in Australia introduced a video-based hazard perception test as part of the licensing process for new drivers. A key validity check for such a test is whether scores are associated with crash involvement. We present data demonstrating that drivers who failed the hazard perception test (based on a ROC curve-derived pass mark) were 25% 95% confidence interval (CI) 6%, 48% more likely to be involved in an active crash (defined as a crash occurring while the driver’s vehicle was moving but they were not engaged in parking or reversing) during a one year period following the test (controlling for driving exposure, age, and sex). Failing drivers were also 17% (95% CI 6%, 29%) more likely to have been involved in active crashes prior to the test, in the period since obtaining their provisional license. These data support the proposal that the hazard perception test is a valid measure of crash-related driving performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND:To interpret blood pressure (BP) data appropriately, healthcare providers need to be knowledgeable of the factors that can potentially impact the accuracy of BP measurement and contribute ...to variability between measurements.
METHODS:A systematic review of studies quantifying BP measurement inaccuracy. Medline and CINAHL databases were searched for empirical articles and systematic reviews published up to June 2015. Empirical articles were included if they reported a study that was relevant to the measurement of adult patients’ resting BP at the upper arm in a clinical setting (e.g. ward or office); identified a specific source of inaccuracy; and quantified its effect. Reference lists and reviews were searched for additional articles.
RESULTS:A total of 328 empirical studies were included. They investigated 29 potential sources of inaccuracy, categorized as relating to the patient, device, procedure or observer. Significant directional effects were found for 27; however, for some, the effects were inconsistent in direction. Compared with true resting BP, significant effects of individual sources ranged from −23.6 to +33 mmHg SBP and −14 to +23 mmHg DBP.
CONCLUSION:A single BP value outside the expected range should be interpreted with caution and not taken as a definitive indicator of clinical deterioration. Where a measurement is abnormally high or low, further measurements should be taken and averaged. Wherever possible, BP values should be recorded graphically within ranges. This may reduce the impact of sources of inaccuracy and reduce the scope for misinterpretations based on small, likely erroneous or misleading, changes.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0
Carboxylic acid reductase (CAR) catalyzes the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes. The enzyme is related to the nonribosomal peptide synthetases, ...consisting of an adenylation domain fused via a peptidyl carrier protein (PCP) to a reductase termination domain. Crystal structures of the CAR adenylation-PCP didomain demonstrate that large-scale domain motions occur between the adenylation and thiolation states. Crystal structures of the PCP-reductase didomain reveal that phosphopantetheine binding alters the orientation of a key Asp, resulting in a productive orientation of the bound nicotinamide. This ensures that further reduction of the aldehyde product does not occur. Combining crystallography with small-angle X-ray scattering (SAXS), we propose that molecular interactions between initiation and termination domains are limited to competing PCP docking sites. This theory is supported by the fact that (R)-pantetheine can support CAR activity for mixtures of the isolated domains. Our model suggests directions for further development of CAR as a biocatalyst.
Phenotypic evolution is often caused by variation in gene expression resulting from altered gene regulatory mechanisms. Genetic variation affecting chromatin remodeling has been identified as a ...potential source of variable gene expression; however, the roles of specific chromatin remodeling factors remain unclear. Here, we address this knowledge gap by examining the relationship between variation in gene expression, variation in chromatin structure, and variation in binding of the pioneer factor Grainy head between imaginal wing discs of two divergent strains of Drosophila melanogaster and their F
hybrid. We find that (1) variation in Grainy head binding is mostly due to sequence changes that act in cis but are located outside of the canonical Grainy head binding motif, (2) variation in Grainy head binding correlates with changes in chromatin accessibility, and (3) this variation in chromatin accessibility, coupled with variation in Grainy head binding, correlates with variation in gene expression in some cases but not others. Interactions among these three molecular layers is complex, but these results suggest that genetic variation affecting the binding of pioneer factors contributes to variation in chromatin remodeling and the evolution of gene expression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy ...alone.
Maps of snow cover serve as early indicators for hydrologic forecasts and as inputs to hydrologic models that inform water management strategies. Advances in snow cover mapping have led to increasing ...accuracy, but unsatisfactory treatment of vegetation's interference when mapping snow has led to maps that have limited utility for water forecasting. Vegetation affects snow mapping because ground surfaces not visible to the satellite produce uncertainty as to whether the ground is snow covered. At nadir, the forest canopy obscures the satellite view below the canopy. At oblique viewing angles, the forest floor is obscured by both the canopy and the projection of tree profiles onto the forest floor. We present a canopy correction method based on Moderate Resolution Imaging Spectroradiometer satellite imagery validated with field observations that mitigates geometric and georegistration issues associated with changing satellite acquisition angles in forested areas. The largest effect from a variable viewing zenith angle on the viewable gap fraction in forested areas occurs in moderately forested areas with 30–40% tree canopy coverage. Cloud cover frequently causes errors in snow identification, with some clouds identified as snow and some snow identified as cloud. A snow‐cloud identification method utilizes a time series of fractional vegetation and rock land‐surface data to flag snow‐cloud identification errors and improve snow‐map accuracy reducing bias by 20% over previous methods. Together, these contributions to snow‐mapping techniques could advance hydrologic forecasting in forested, snow‐dominated basins that comprise an estimated one fifth of Northern Hemisphere snow‐covered areas.
Plain Language Summary
Mapping snow cover extent informs water resources stored in the winter snowpack, providing important information for planning how and when to utilize available water. Tree canopies shield the forest floor and hinder the determination of snow‐covered area in vegetated terrain from above, where satellites view the Earth's surface. Moreover, satellites that scan the surface (like the Moderate Resolution Imaging Spectroradiometer) are most often not directly overhead, and as the view from the satellite to the surface slants, trees obscure a greater portion of the land surface that a satellite can “see,” especially where trees are tall, adding uncertainty to the satellite‐based maps. This effect is greatest in forests where 30–40% of the land area is covered by tree canopy and has little effect in very dense forests where most of the forest floor is obscured already. Here we present a method to accommodate the stretched and hidden forest footprint when a satellite is not directly overhead. A new method for identifying snow‐mapping errors caused by clouds is also presented by flagging unusually large changes in the non‐snow surfaces over sequential images. These methodological advancements are important because snow‐melt water comprises a major portion of the water supply in many regions where humans live.
Key Points
The canopy correction methodology improves remotely sensed snow mapping accuracy in forested environments, reducing bias by 20%
A novel cloud detection algorithm that uses fractional vegetation and rock coverage can reduce snow‐cloud identification errors
Improved performance over previous snow mapping approaches enable melt out date identification within days of actual snow disappearance
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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