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BackgroundTumor infiltrating lymphocytes (TILs) are prognostic in triple-negative breast cancer, but not estrogen receptor (ER) positive cancers which comprise 70%–80% of breast cancers. This is due to the relatively low immune infiltration in ER-positive tumors. However, few studies have explored the prognostic impact of lower abundance TILs evaluated using spatial methods. The objective of this study was to explore whether the distribution of lymphocytes with respect to tumor cells predicts prognosis. Methods and findingsIn this retrospective cohort study, we used multiplex immunofluorescent (IF)-stained images of tissue microarray cores (stained for cytokeratin [Ck], CD8, and FoxP3) obtained from 1,467 study participants to compute distance-based visual morphometry for epithelial and immune cells, including two new metrics,proximityandconsistency. Proximity and consistency are defined as functions of the mean and variance of nearest neighbor distances between Ck+ tumor cells and CD8+ T cells. Prognostic significance of proximity and consistency were compared to lymphocyte counts using log-rank tests of differences in Kaplan–Meier survival curves and Cox proportional hazards models. Better recurrence-free survival (RFS) was observed for both ER+ and ER− breast cancers with high proximity and consistency of CD8+ T cells. Among ER− breast cancers, proximity had the highest RFS hazard ratio (HR 1.84, 95% CI [1.18, 2.87];p = 0.0069) compared to count and consistency. Among ER-positive participants, RFS hazard ratios for proximity and consistency were 2.04 (95% CI [1.39, 2.98];p = 0.0003) and 1.82 (95% CI [1.23, 2.69];p = 0.0026), respectively. These associations were stronger than those observed for lymphocyte count (HR 1.35, 95% CI [0.92, 1.98];p = 0.1289). Independent prognostic value was demonstrated by controlling clinical and demographic variables such as age, tumor grade, stage, ER status, progesterone receptor status, and human epidermal growth factor receptor 2 status. These IF-derived spatial metrics were also associated with established TILs metrics and RNA expression-based measures of tumor adaptive immune response. Though these results are promising, our exploration of the tumor immune microenvironment was limited by the small number of immune markers available for our data. ConclusionsSpatial characteristics described by proximity and consistency are frequently associated with recurrence irrespective of ER status. The prognostic significance of proximity in ER+ breast cancer implies that spatial parameters may identify individuals who would benefit from immune therapy; up to 75% of breast cancers experience T cell proximity suggestive of immune susceptibility. 

ABSTRACT The rising threat of marine heatwaves has led to numerous predictions that coral reefs, especially those near the Equator, will be severely degraded by the end of the current century. Yet, environmental conditions near the Equator may regionally moderate coral bleaching by reducing thermal stress during marine heatwaves. We deployed a Bayesian spatio‐temporal model over Earth to examine which environmental conditions may characterize marine‐heatwave refugia for coral reefs by testing the relationship between the severity of coral bleaching and a suite of temperature, hydrodynamic, topographic, atmospheric, and biological variables. The model considered the severity of coral bleaching as the proportion of bleached hard corals during 30,266 coral‐reef surveys conducted at 8728 sites, at depths of up to 20 m, and located between 35° north and south of the Equator across 81 countries, from 2002 to 2020. Except for the eastern Pacific Ocean, the severity of coral bleaching during marine heatwaves was lower on equatorial reefs than on higher‐latitude reefs, suggesting that marine‐heatwave refugia for corals have been concentrated in the equatorial Coral Triangle region. Indeed, equatorial reefs in the Coral Triangle were, on average, exposed to the weakest marine heatwaves, potentially because they were shielded from extreme insolation by frequent cloud coverage in the Intertropical Convergence Zone. Coral bleaching may also be moderated during marine heatwaves on reefs that experience high wave energy, high current velocity, high cloud frequency, or turbidity. Coral bleaching was also less severe on reefs that historically endured frequent heatwaves than on reefs that were naïve to thermal stress. Based on modern and historical responses of coral reefs to acute thermal stress, we hypothesize that many equatorial reefs will continue to serve as marine‐heatwave refugia for corals. 

Abstract Corals are being increasingly subjected to marine heatwaves. Theory suggests that increasing the intensity of disturbances reduces recovery rates, which inspired us to examine the recovery rates of coral cover following marine heatwaves, cyclones, and other disturbances at 1921 study sites, in 58 countries and three oceans, from 1977 to 2020. In the Atlantic Ocean, coral cover has decreased fourfold since the 1970s, and recovery rates following disturbances have been relatively slow, except in the Antilles. By contrast, reefs in the Pacific and Indian Oceans have maintained coral cover and recovery rates over time. There were positive relationships between rates of coral recovery and prior cyclone and heatwave frequency, and negative relationships between rates of coral recovery and macroalgae cover and distance to shore. A recent increase in the variance in recovery rates in some ecoregions of the Pacific and Indian Oceans suggests that some reefs in those ecoregions may be approaching a phase shift. While marine heatwaves are increasing in intensity and frequency, our results suggest that regional and local conditions influence coral recovery rates, and therefore, effective local management efforts can help reefs recover from disturbances. 

ABSTRACT We present the analysis of the absorption troughs of six outflows observed in quasar SDSS J1130 + 0411 ($$z$$ ≈ 3.98) with radial velocities ranging from −2400 to $$-15\, 400$$ km s−1. These spectra were taken with the Very Large Telescope/Ultraviolet and Visual Echelle Spectrograph over the rest-frame wavelength range of 1135–1890 Å. In the main outflow system ($$v$$ ≈ −3200 km s−1), we identify Fe ii and several Fe ii* absorption troughs, as well as Si ii and Si ii* troughs, which we use to determine the electron number density $$\log n_e = 2.6_{-0.7}^{+0.8}$$ cm−3. Using the column densities of these and other ions, we determine a photoionization solution with hydrogen column density $$\log N_H = 21.44_{-0.33}^{+0.24}$$ cm−2 and ionization parameter $$\log U_H = -1.75_{-0.45}^{+0.28}$$. From these values, we derive the distance $$R = 16_{-11}^{+23}$$ kpc, the average mass flow rate $$\dot{M} = 4100_{-2400}^{+6600}$$ M⊙ yr−1, and the kinetic luminosity $$\log \dot{E}_k = 46.13_{-0.37}^{+0.41}$$ erg s−1. This $$\dot{E}_k$$ is $$1.4_{-0.8}^{+2.2}$$ per cent of the quasar’s Eddington luminosity, and therefore contributes significantly to AGN feedback. 

Abstract Xylella fastidiosais a bacterium that infects crops like grapevines, coffee, almonds, citrus and olives. There is little understanding of the genes that contribute to plant resistance, the genomic architecture of resistance, and the potential role of climate in shaping resistance, in part because major crops like grapevines (Vitis vinifera) are not resistant to the bacterium. Here we study a wild grapevine species,V. arizonica, that segregates for resistance. Using genome-wide association, we identify candidate resistance genes. Resistance-associated kmers are shared with a sister species ofV. arizonicabut not with more distant species, suggesting that resistance evolved more than once. Finally, resistance is climate dependent, because individuals from low ( < 10 °C) temperature locations in the wettest quarter were typically susceptible to infection, likely reflecting a lack of pathogen pressure in colder climates. In fact, climate is as effective a predictor of resistance phenotypes as some genetic markers. We extend our climate observations to additional crops, predicting that increased pathogen pressure is more likely for grapevines and almonds than some other susceptible crops. 

ABSTRACT We analyse the VLT/UVES spectrum of the quasar SDSS J143907.5-010616.7, retrieved from the UVES Spectral Quasar Absorption Database. We identify two outflow systems in the spectrum: a mini broad absorption line (mini-BAL) system and a narrow absorption line (NAL) system. We measure the ionic column densities of the mini-BAL ($$v$$ = −1550 km s−1) outflow, which has excited state absorption troughs of $${\rm Fe\, \rm {\small {ii}}}$$. We determine that the electron number density $$\log {n_e}=3.4^{+0.1}_{-0.1}$$, based on the ratios between the excited and ground state abundances of $${\rm Fe\, \rm {\small {ii}}}$$, and find the kinetic luminosity of the outflow to be $${\lesssim}0.1\,\hbox{per cent}$$ of the quasar’s Eddington luminosity, making it insufficient to contribute to AGN feedback. 

Domesticated grapevines spread to Europe around 3,000 years ago. Previous studies have revealed genomic signals of introgression from wild to cultivated grapes in Europe, but the time, mode, genomic pattern, and biological effects of these introgression events have not been investigated. Here, we studied resequencing data from 345 samples spanning the distributional range of wild (Vitis viniferassp.sylvestris) and cultivated (V. viniferassp.vinifera) grapes. Based on machine learning–based population genetic analyses, we detected evidence for a single domestication of grapevine, followed by continuous gene flow between European wild grapes (EU) and cultivated grapes over the past ~2,000 y, especially from EU to wine grapes. We also inferred that soft-selective sweeps were the dominant signals of artificial selection. Gene pathways associated with the synthesis of aromatic compounds were enriched in regions that were both selected and introgressed, suggesting EU wild grapes were an important resource for improving the flavor of cultivated grapes. Despite the potential benefits of introgression in grape improvement, the introgressed fragments introduced a higher deleterious burden, with most deleterious SNPs and structural variants hidden in a heterozygous state. Cultivated wine grapes have benefited from adaptive introgression with wild grapes, but introgression has also increased the genetic load. In general, our study of beneficial and harmful effects of introgression is critical for genomic breeding of grapevine to take advantage of wild resources. 

Abstract Earth's core has produced a global magnetic field for at least the last 3.5 Gyrs, presently sustained by inner core (IC) growth. Models of the core with high thermal conductivity suggest potentially insufficient power available for the geodynamo prior to IC formation ∼1 Ga. Precipitation of silicon from the liquid core might offer an alternative power source for the ancient magnetic field, although few estimates of the silicon partition coefficient exist for conditions of the early core. We present the first ab initio determination of the silicon partition coefficient at core‐mantle boundary conditions and use these results to confirm a thermodynamic description of partitioning that is integrated into a model of coupled core‐mantle thermal evolution. We show that models including precipitation of silicon can satisfy constraints of IC size, mantle convective heat flux, mantle temperature and a persistent ancient geodynamo, and favor an oxygen poor initial core composition.