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At least 649 records · Page 36

Do Genetic Drift and Gene Flow Affect the Geographic Distribution of Female Plants in Gynodioecious Lobelia siphilitica?

Variation in population sex ratio is particularly pronounced in gynodioecious angiosperms. Extremely high female frequencies in gynodioecious populations cannot be readily explained by selective forces alone. To assess the contributions of drift and gene flow to extreme sex-ratio variation, we documented sex ratio and population size in 92 populations of Lobelia siphilitica across its range and genotyped plants using plastid and nuclear genetic markers. Similarity in spatial patterns of genetic and demographic variables may suggest that drift and/or gene flow have contributed to population sex-ratio variation in L. siphilitica. We found strong spatial structuring of extremely high female frequencies: populations with >50% female plants are restricted to the south–central portion of the range. However, we did not detect any spatial structuring in population size nor metrics of genetic diversity, suggesting that extreme variation in female frequency is not strongly affected by drift or gene flow. Extreme sex-ratio variation is frequently observed in gynodioecious plants, but its causes are difficult to identify. Further investigation into mechanisms that create or maintain the spatial structure of sex ratios in gynodioecious species will provide much needed insight.

54 ENVIRONMENTAL SCIENCES↗

Far-ultraviolet to FIR Spectral-energy Distribution Modeling of the Stellar Formation History of the M31 Bulge

M31 is being surveyed at far- and near-ultraviolet with the UVIT telescope on AstroSat. The central bulge of M31 was observed in the N279N (275–280 nm), N219M (200–240 nm), F172M (160–185 nm), F169M (145–175 nm), and F148W (120–180 nm) filters. These images are made publicly available here. The UVIT data are supplemented with Sloan Digital Sky Survey data in optical, Spitzer data in near-infrared and Herschel data in mid- and far-infrared. The resulting far-ultraviolet to IR spectral-energy distributions for the bulge and for 10 subregions, are modeled using combinations of simple stellar populations and with CIGALE models. We find a dominant old (10–12 Gyr) metal-rich ([Z/H] ~ 0.3) population and a younger (600 Myr) solar abundance ([Z/H] ~ 0) population throughout the bulge. For the innermost 120" we find an additional very young (25 Myr) metal-poor ([Z/H] ~ –0.7) population. The results are consistent with the most recent stellar population studies of the bulge, which find the two populations for the whole bulge and a third young population in the innermost bulge.

79 ASTRONOMY AND ASTROPHYSICS↗

Size and Spectroscopic Evolution of HectoMAP Quiescent Galaxies

Abstract The HectoMAP survey provides a complete, mass-limited sample of 30,231 quiescent galaxies with i -band Hyper Suprime-Cam Subaru Strategic Program (HSC SSP) imaging that spans the redshift range 0.2 < z < 0.6. We combine half-light radii based on HSC SSP imaging with redshifts and D n 4000 to explore the size–mass relation, R e = A × M * α , and its evolution for the entire HectoMAP quiescent population and for two subsets of the data. Newcomers with 1.5 < D n 4000 < 1.6 at each redshift show a steeper increase in A as the universe ages than the population that descends from galaxies that are already quiescent at the survey limit, z ∼ 0.6 (the resident population). In broad agreement with previous studies, evolution in the size–mass relation both for the entire HectoMAP sample and for the resident population (but not for the newcomers alone) is consistent with minor merger driven growth. For the resident population, the evolution in the size–mass relation is independent of the population age at z ∼ 0.6. The contrast between the sample of newcomers and the resident population provides insight into the role of commonly termed “progenitor bias” on the evolution of the size–mass relation.

79 ASTRONOMY AND ASTROPHYSICS↗

DESI Survey Validation Spectra Reveal an Increasing Fraction of Recently Quenched Galaxies at z ∼ 1

Abstract We utilize ∼17,000 bright luminous red galaxies (LRGs) from the novel Dark Energy Spectroscopic Instrument Survey Validation spectroscopic sample, leveraging its deep (∼2.5 hr galaxy −1 exposure time) spectra to characterize the contribution of recently quenched galaxies to the massive galaxy population at 0.4 < z < 1.3. We use Prospector to infer nonparametric star formation histories and identify a significant population of recently quenched galaxies that have joined the quiescent population within the past ∼1 Gyr. The highest-redshift subset (277 at z > 1) of our sample of recently quenched galaxies represents the largest spectroscopic sample of post-starburst galaxies at that epoch. At 0.4 < z < 0.8, we measure the number density of quiescent LRGs, finding that recently quenched galaxies constitute a growing fraction of the massive galaxy population with increasing look-back time. Finally, we quantify the importance of this population among massive ( log ( M ⋆ / M ⊙ ) > 11.2) LRGs by measuring the fraction of stellar mass each galaxy formed in the gigayear before observation, f 1 Gyr . Although galaxies with f 1 Gyr > 0.1 are rare at z ∼ 0.4 (≲0.5% of the population), by z ∼ 0.8, they constitute ∼3% of massive galaxies. Relaxing this threshold, we find that galaxies with f 1 Gyr > 5% constitute ∼10% of the massive galaxy population at z ∼ 0.8. We also identify a small but significant sample of galaxies at z = 1.1–1.3 that formed with f 1 Gyr > 50%, implying that they may be analogs to high-redshift quiescent galaxies that formed on similar timescales. Future analysis of this unprecedented sample promises to illuminate the physical mechanisms that drive the quenching of massive galaxies after cosmic noon.

79 ASTRONOMY AND ASTROPHYSICS↗

LandScan Global 2023: Silver Edition

For a quarter of a century, the LandScan Global (LSG) project has annually released a global, high-resolution gridded population dataset representing the ambient or unwarned population at a 30 arcsecond resolution. LSG supports a range of applications such as emergency management, disaster response, and human health and security for understanding populations at risk. The 2023 release of LSG, the LandScan Silver Edition, represents a major methodological leap forward while also leveraging previous knowledge—the previous year was the baseline for the current annual update carrying forward valuable knowledge of the built environment for the past quarter century—to train the machine learning models. Compared with annual releases over the past 24years, multiple advancements were made to different aspects of the methodology to achieve reproducibility, transparency, and consistent global propagation of solutions to modeling or population distribution issues identified during the review process. These novel changes include incorporation of the latest available geospatial inputs across the globe, machine learning models instead of manual modifications, population feature importance analysis, open-source solutions vs. proprietary software, generation of multiple global versions, analytic validations, and human-in-the-loop revisions to produce the final version. Additionally, algorithms—such as anomaly detection—were introduced to quickly identify areas of focus to develop a new and robust systematic review. Significant changes in modeled population distributions were observed between the 2022 and 2023 releases, largely attributable to improvements in data and methods and discussed thoroughly within this report. In summation, the LandScan Silver Edition leverages the best of the past quarter century of LSG legacy knowledge and continues a tradition of applying cutting-edge enhancements to serve as a new benchmark for accurate, actionable gridded population data

Lebakula, Viswadeep↗

The COMBS Survey – III. The chemodynamical origins of metal-poor bulge stars

The characteristics of the stellar populations in the Galactic bulge inform and constrain the Milky Way’s formation and evolution. The metal-poor population is particularly important in light of cosmological simulations, which predict that some of the oldest stars in the Galaxy now reside in its centre. The metal-poor bulge appears to consist of multiple stellar populations that require dynamical analyses to disentangle. In this work, we undertake a detailed chemodynamical study of the metal-poor stars in the inner Galaxy. Using R ~ 20000 VLT/GIRAFFE spectra of 319 metal-poor (-2.55 dex ≤ [Fe/H] ≤ 0.83 dex, with $\overline{[Fe/H]}$ = -0.84 dex) stars, we perform stellar parameter analysis and report 12 elemental abundances (C, Na, Mg, Al, Si, Ca, Sc, Ti, Cr, Mn, Zn, Ba, and Ce) with precisions of ≈0.10 dex. Based on kinematic and spatial properties, we categorize the stars into four groups, associated with the following Galactic structures: the inner bulge, the outer bulge, the halo, and the disc. We find evidence that the inner and outer bulge population is more chemically complex (i.e. higher chemical dimensionality and less correlated abundances) than the halo population. This result suggests that the older bulge population was enriched by a larger diversity of nucleosynthetic events. We also find one inner bulge star with a [Ca/Mg] ratio consistent with theoretical pair-instability supernova yields and two stars that have chemistry consistent with globular cluster stars.

79 ASTRONOMY AND ASTROPHYSICS↗

Efficacy of Hair Total Mercury Content as a Biomarker of Methylmercury Exposure to Communities in the Area of Artisanal and Small-Scale Gold Mining in Madre de Dios, Peru

Total mercury content (THg) in hair is an accepted biomarker for chronic dietary methylmercury (MeHg) exposure. In artisanal and small-scale gold mining (ASGM) communities, the validity of this biomarker is questioned because of the potential for contamination from inorganic mercury. As mining communities may have both inorganic and organic mercury exposures, the efficacy of the hair-THg biomarker needs to be evaluated, particularly as nations begin population exposure assessments under their commitments to the Minamata Convention. We sought to validate the efficacy of hair THg for public health monitoring of MeHg exposures for populations living in ASGM communities. We quantified both THg and MeHg contents in hair from a representative subset of participants (N = 287) in a large, population-level mercury exposure assessment in the ASGM region in Madre de Dios (MDD), Peru. We compared population MeHg-THg correlations and %MeHg values with demographic variables including community location, sex, occupation, and nativity. We observed that hair MeHg-THg correlations were high (r > 0.7) for all communities, regardless of location or nativity. Specifically, for individuals within ASGM communities, 81% (121 of 150 total) had hair THg predominantly in the form of MeHg (i.e., >66% of THg) and reflective of dietary exposure to mercury. Furthermore, for individuals with hair THg exceeding the U.S. EPA threshold (1.0 μg/g), 88 out of 106 (83%) had MeHg as the predominant form. As a result, had urine THg solely been used for mercury exposure monitoring, approximately 59% of the ASGM population would have been misclassified as having low mercury exposure. Our results support the use of hair THg for monitoring of MeHg exposure of populations in ASGM settings where alternative biomarkers of MeHg exposure are not feasible.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

The Impact of Variability in Patient Exposure During Premarket Clinical Development on Postmarket Safety Outcomes

We characterized the size of the premarket safety population for 278 small-molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by the US Food and Drug Administration (FDA) between October 1, 2002, and December 31, 2014, evaluating the relationship of premarket safety population size to regulatory characteristics and postmarket safety outcomes. The median size of the safety population was 1,044, and was lower for NTBs than NMEs (median: 920 vs. 1,138, P = 0.04), orphan products than nonorphan products (393 vs. 1,606, P < 0.001), and for products with fast-track designation (617 vs. 1,455, P < 0.001), priority review (630 vs. 1,735, P < 0.001), and accelerated approval (475 vs. 1,164, P < 0.001), than products without that designation. The median number of postmarket safety label updates and issues added to the label were higher with larger premarket exposure among nonorphan products, but not among orphan products. Products with accelerated approval using a surrogate end point had a higher median number of safety issues added to the label than those with full approval, but this did not vary with the size of the safety population; fast-track and priority review were not associated with the number of safety issues added to the label. Here, a smaller safety population size was associated with a longer time to first safety outcome for nonorphan products but not orphan products. For orphan and nonorphan products combined, smaller premarket safety population size is not associated with the number or timing of postmarket safety outcomes, regardless of expedited program participation.

60 APPLIED LIFE SCIENCES↗

Identification of quantitative trait loci for sorghum leaf blight resistance

Sorghum leaf blight and northern corn leaf blight, both caused by Exserohilum turcicum {(Pass.) K. J. Leonard and Suggs [syn. Setosphaeria turcica (Luttr.) K. J. Leonard and Suggs.]}, are major diseases of sorghum [Sorghum bicolor (L.) Moench] and maize (Zea mays L.), respectively. Examining the genetic architecture of resistance in sorghum will lead to a better understanding of the relationship between resistance in sorghum and maize, which can ultimately enhance management options in both crops. In 2018 and 2019, we evaluated two sorghum recombinant inbred line (RIL) populations for resistance to E. turcicum. The BTx623 × IS3620C and BTx623 × SC155 populations consisted of 235 and 81 RILs, respectively. Resistance in both populations was moderately to highly heritable. We identified a total of six quantitative trait loci (QTL) across the two populations. Three QTL with small- to moderate-effect sizes were identified in the BTx623 × IS3620C population. Three QTL, including a large-effect QTL on chromosome three that explained 24% of the variation, were identified in the BTx623 × SC155 population. We compared the identified QTL with the position of northern corn leaf blight candidate genes and found eight candidate resistance gene orthologs that colocalize with the sorghum leaf blight QTL. There were also several nucleotide-binding leucine-rich repeat encoding genes within the candidate intervals. Understanding host resistance in multiple species furthers our understanding of the Exserohilum turcicum patho-system.

59 BASIC BIOLOGICAL SCIENCES↗

Achieving Productivity to Recover and Restore Columbia River Stream-Type Chinook Salmon Relies on Increasing Smolt-To-Adult Survival

Abstract We analyzed and compared productivity and survival rates of populations of stream-type Chinook Salmon Oncorhynchus tshawytscha from the upper and middle ranges of their distribution in the Columbia River basin. These two groups of populations undergo vastly different exposures during migration through the Federal Columbia River Power System (FCRPS). Declines of the Snake River populations, listed as threatened under the U.S. Endangered Species Act, have been associated with the development and operation of the FCRPS. In contrast, John Day River stream-type Chinook Salmon populations, which were less affected by the FCRPS, have declined to a lesser extent and are not listed. Smolt-to-adult survival rates (SARs) accounted for a majority of the variation in life cycle survival rates of Snake River Chinook Salmon. Productivity declined to 13% and 44% of historical productivity levels for Snake River and John Day River populations, respectively. A synthesis of previous studies contrasting anthropogenic impacts between the two regions supports the conclusion that FCRPS impacts explain the large difference in population productivity. Our results suggest that SARs of 4% would result in an expected productivity of up to 70% of historical levels (a SAR level consistent with regional restoration objectives). The SARs have been shown to be highly influenced by conditions within the FCRPS (e.g., water velocity and passage through dam powerhouses). Marine conditions also influence SARs; however, meaningful management actions are only available to affect conditions within the FCRPS. Given the importance of SARs to overall life cycle productivity, recovery and restoration strategies need to prioritize actions that have potential to substantially increase SARs by addressing the significant impacts of main-stem dams. This study highlights the importance of considering river management options in the face of increasingly variable and warming ocean conditions.

Petrosky, Charles E.↗

Efficacy of one-time rotenone application for Westslope Cutthroat Trout restoration in Boulder Creek, Montana

Abstract Objective Although piscicides are an important tool for native fish management, our understanding of native fish population dynamics posttreatment (i.e., in putatively vacant habitat) is limited. Methods Here, we describe long-term trends in size and abundance of Cutthroat Trout Oncorhynchus clarkii in Lower Boulder Lake and Boulder Creek (Montana). Result No significant differences were found before and after treatment with rotenone in mean length and population density in Boulder Creek. Posttreatment genetic samples from Boulder Lake and upper Boulder Creek consisted entirely of the Westslope Cutthroat Trout Oncorhynchus clarkii lewisi used to refound the population. Middle and lower Boulder Creek genetic samples contained 99.4% and 98.4% Westslope Cutthroat Trout, indicating that some nonnative (Yellowstone Cutthroat Trout Oncorhynchus clarkii bouvieri hybrid) fish survived the treatment. Population demographics showed robust recovery posttreatment; however, genetic results revealed the limitations of a one-time treatment—that is, an incomplete fish kill. Conclusion We demonstrate that Cutthroat Trout populations achieve recovery after rotenone treatment in the long term, but one-time rotenone treatments on large drainages often fail to totally eradicate populations. Therefore, managers should plan on multiple treatments and utilize environmental DNA to help achieve total removal of target species.

Lampton, Jared↗

Surveying Grassland Islands: the genetics and performance of Appalachian switchgrass (Panicum virgatum L.) collections

The interior Southeastern United States could contain novel germplasm for the bioenergy crop switchgrass due to its diverse habitats and geographic location between genetic subpopulations (Atlantic, Midwest, and Gulf). Collections from this region could accelerate breeding progress, contribute to conservation efforts, and improve understanding of isolated grasslands in the region. This study located 22 sites in the Midsouth region and obtained 1,521,210 single nucleotide polymorphism markers of 202 individuals through genotype-by-sequencing. Here, individuals were evaluated for flowering time, winter survival and tiller number. Comparison to a national diversity panel revealed that branches of two major subpopulations occur in the region with two levels of polyploidy: Atlantic tetraploids and Midwest octoploids. Two locations contained admixed octoploid individuals with Midwest and Gulf genetics. Field performance of the Midwest octoploids conformed with prior reported performance of the Midwest subpopulation, although three sites contained promising late flowering traits. The Atlantic tetraploids had moderate winter survival, short stature, and anomalously early flowering. Atlantic populations mostly occurred in marginal sites and their morphological and flowering time adaptations may be a resource conservation strategy. Demographic inference of historical effective population size variation in a subset of tetraploid locations indicated a widespread recent decline in effective population size. This pattern is consistent with isolation of these switchgrass communities from larger populations and is further supported by evidence of inbreeding within the populations (F I = 0.18). The populations documented in this study contain novel genetic diversity and adaptations to a range of marginal habitats. Therefore, this study provides a new source of germplasm for future breeding and conservation programs.

59 BASIC BIOLOGICAL SCIENCES↗

Estimating the Benefits of Sustainable Aviation Fuel Usage at Chicago O’Hare International Airport on Ultrafine Particle Exposure and Mortalities Reductions

The expanding commercial aviation sector necessitates diverse energy sources, and sustainable aviation fuels (SAFs) have emerged as a promising option. Widespread SAF adoption can help meet transportation fuel demand and offer health benefits for people residing near airports or along airport landing and takeoff (LTO) pathways, where elevated levels of aircraft-derived air pollution often exist. Blending SAF with traditional jet fuels can reduce ultrafine particle (UFP) emissions, which may improve health of near airport population. We analyzed a population of about 8 million people in 1925 census tracts around the Chicago O’Hare International Airport (ORD). We conducted a risk assessment to estimate anticipated UFP reductions for three adoption scenarios using blends of traditional jet fuels with 5, 25, and 50% SAF across all flights landing and taking off from ORD. We calculated baseline estimates of UFP emissions using ORD flight data, a dispersion model, and a calibration function derived from mobile monitoring data. We used this baseline UFP emission profile across the study area to estimate population-weighted UFP, as well as the attributable case reductions (ACRs) and attributable mortality rate reductions (AMRRs) across the demographic distribution around the airport, based on the SAF blending scenarios. We found a positive association of SAF blending with UFP reductions, particularly near the airport and along LTO flight pathways. Our study showed that the population-weighted UFP across different demographics was similar. ACRs were largely dependent on individual demographic populations, while AMRRs for all populations were relatively similar, with an estimated 0.3 (95% range: 0.2−0.3), 1.1 (0.9−1.4), and 1.8 (1.5−2.2) fewer mortalities per 100,000 people per year expected with the adoption of 5, 25, and 50% SAF blends, respectively. This study indicates that communities near ORD, across a range of demographics, may benefit similarly from SAF adoption, thus highlighting how SAF adoption may offer an opportunity to improve health outcomes like aviation UFP-related mortalities around airports.

10 SYNTHETIC FUELS↗

Quantifying the Role of EMIC Wave Scattering During the 27 February 2014 Storm by RAM–SCB Simulations

Electromagnetic Ion Cyclotron (EMIC) wave scattering has been proved to be responsible for the fast loss of both radiation belt (RB) electrons and ring current (RC) protons. However, its role in the concurrent dropout of these two co–located populations remains to be quantified. In this work, we study the effect of EMIC wave scattering on both populations during the 27 February 2014 storm by employing the global physics–based RAM–SCB model. Throughout this storm event, MeV RB electrons and 100s keV RC protons experienced simultaneous dropout following the occurrence of intense EMIC waves. By implementing data–driven initial and boundary conditions, we perform simulations for both populations through the interplay with EMIC waves and compare them against Van Allen Probes observations. Notably, the results indicate that by including EMIC wave scattering loss, especially by the He–band EMIC waves, the model aligns closely with data for both populations. Additionally, we investigate the simulated pitch angle distributions (PADs) for both populations. Including EMIC wave scattering in our model predicts a 90° peaked PAD for electrons with stronger losses at lower pitch angles, while protons exhibit an isotropic PAD with enhanced losses at pitch angles above 40°. Furthermore, our model predicts considerable precipitation of both particle populations, predominantly confined to the afternoon to midnight sector (12 hr < MLT < 24 hr) during the storm's main phase, corresponding closely with the presence of EMIC waves.

79 ASTRONOMY AND ASTROPHYSICS↗

Deep neural network improves the estimation of polygenic risk scores for breast cancer

Polygenic risk scores (PRS) estimate the genetic risk of an individual for a complex disease based on many genetic variants across the whole genome. Here, we compared a series of computational models for estimation of breast cancer PRS. A deep neural network (DNN) was found to outperform alternative machine learning techniques and established statistical algorithms, including BLUP, BayesA, and LDpred. In the test cohort with 50% prevalence, the Area Under the receiver operating characteristic Curve (AUC) were 67.4% for DNN, 64.2% for BLUP, 64.5% for BayesA, and 62.4% for LDpred. BLUP, BayesA, and LPpred all generated PRS that followed a normal distribution in the case population. However, the PRS generated by DNN in the case population followed a bimodal distribution composed of two normal distributions with distinctly different means. This suggests that DNN was able to separate the case population into a high-genetic-risk case subpopulation with an average PRS significantly higher than the control population and a normal-genetic-risk case subpopulation with an average PRS similar to the control population. This allowed DNN to achieve 18.8% recall at 90% precision in the test cohort with 50% prevalence, which can be extrapolated to 65.4% recall at 20% precision in a general population with 12% prevalence. Interpretation of the DNN model identified salient variants that were assigned insignificant p values by association studies, but were important for DNN prediction. These variants may be associated with the phenotype through nonlinear relationships.

59 BASIC BIOLOGICAL SCIENCES↗

Proteome specialization of anaerobic fungi during ruminal degradation of recalcitrant plant fiber

The rumen harbors a complex microbial mixture of archaea, bacteria, protozoa, and fungi that efficiently breakdown plant biomass and its complex dietary carbohydrates into soluble sugars that can be fermented and subsequently converted into metabolites and nutrients utilized by the host animal. While rumen bacterial populations have been well documented, only a fraction of the rumen eukarya are taxonomically and functionally characterized, despite the recognition that they contribute to the cellulolytic phenotype of the rumen microbiota. To investigate how anaerobic fungi actively engage in digestion of recalcitrant fiber that is resistant to degradation, we resolved genome-centric metaproteome and metatranscriptome datasets generated from switchgrass samples incubated for 48 h in nylon bags within the rumen of cannulated dairy cows. Across a gene catalog covering anaerobic rumen bacteria, fungi and viruses, a significant portion of the detected proteins originated from fungal populations. Intriguingly, the carbohydrate-active enzyme (CAZyme) profile suggested a domain-specific functional specialization, with bacterial populations primarily engaged in the degradation of hemicelluloses, whereas fungi were inferred to target recalcitrant cellulose structures via the detection of a number of endo- and exo-acting enzymes belonging to the glycoside hydrolase (GH) family 5, 6, 8, and 48. Notably, members of the GH48 family were amongst the highest abundant CAZymes and detected representatives from this family also included dockerin domains that are associated with fungal cellulosomes. A eukaryote-selected metatranscriptome further reinforced the contribution of uncultured fungi in the ruminal degradation of recalcitrant fibers. These findings elucidate the intricate networks of in situ recalcitrant fiber deconstruction, and importantly, suggest that the anaerobic rumen fungi contribute a specific set of CAZymes that complement the enzyme repertoire provided by the specialized plant cell wall degrading rumen bacteria.

Hagen, Live↗

Accuracy of environmental tracers and consequences for determining the Type Ia supernova magnitude step

Type Ia Supernovae (SNe Ia) are standardizable candles that allow us to measure the recent expansion rate of the Universe. Due to uncertainties in progenitor physics, potential astrophysical dependencies may bias cosmological measurements if not properly accounted for. The dependency of the intrinsic luminosity of SNe Ia with their host-galaxy environment is often used to standardize SNe Ia luminosity and is commonly parameterized as a step function. This functional form implicitly assumes two-populations of SNe Ia. In the literature, multiple environmental indicators have been considered, finding different, sometimes incompatible, step function amplitudes. We compare these indicators in the context of a two-populations model, based on their ability to distinguish the two populations. We show that local Hα-based specific star formation rate (lsSFR) and global stellar mass are better tracers than, for instance, host galaxy morphology. We show that tracer accuracy can explain the discrepancy between the observed SNe Ia step amplitudes found in the literature. Using lsSFR or global mass to identify the two populations can explain all other observations, though lsSFR is favoured. As lsSFR is strongly connected to age, our results favour a prompt and delayed population model. In any case, there exists two populations that differ in standardized magnitude by at least 0.121 ± 0.010 mag.

79 ASTRONOMY AND ASTROPHYSICS↗

Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane

The small GTPase KRAS is localized at the plasma membrane where it functions as a molecular switch, coupling extracellular growth factor stimulation to intracellular signaling networks. In this process, KRAS recruits effectors, such as RAF kinase, to the plasma membrane where they are activated by a series of complex molecular steps. Defining the membrane-bound state of KRAS is fundamental to understanding the activation of RAF kinase and in evaluating novel therapeutic opportunities for the inhibition of oncogenic KRAS-mediated signaling. We combined multiple biophysical measurements and computational methodologies to generate a consensus model for authentically processed, membrane-anchored KRAS. In contrast to the two membrane-proximal conformations previously reported, we identify a third significantly populated state using a combination of neutron reflectivity, fast photochemical oxidation of proteins (FPOP), and NMR. In this highly populated state, which we refer to as “membrane-distal” and estimate to comprise ~90% of the ensemble, the G-domain does not directly contact the membrane but is tethered via its C-terminal hypervariable region and carboxymethylated farnesyl moiety, as shown by FPOP. Subsequent interaction of the RAF1 RAS binding domain with KRAS does not significantly change G-domain configurations on the membrane but affects their relative populations. Overall, our results are consistent with a directional fly-casting mechanism for KRAS, in which the membrane-distal state of the G-domain can effectively recruit RAF kinase from the cytoplasm for activation at the membrane.

KRAS↗