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Commensal Nakaseomyces glabratus migrates into prostate tumors to accelerate cancer progression
Item type: Journal Article
Lai P.; Liu L.; Pernigoni N.; et al. (2026)
Recent studies demonstrate that the gut mycobiota plays a key role in several tumors. However, the contribution of commensal fungi to prostate cancer initiation and progression remains understudied. Here we find that Nakaseomyces glabratus is enriched in fecal, blood and tumor samples of patients with castration-resistant prostate cancer, correlating with patients’ poor overall survival. Oral administration of N. glabratus to castrated mice accelerated cancer progression by promoting infiltration and activation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, androgen deprivation therapy increases intestinal permeability, resulting in the leakage of N. glabratus from the gut to the tumor site, activating PMN-MDSCs via the Dectin-2 receptor. Treatment of mice with a negatively charged intestinal hydrogel blocks N. glabratus translocation to tumor, reducing PMN-MDSCs’ intratumoral infiltration and activation. Taken together, these findings reveal that the gut-to-tumor translocation of N. glabratus contributes to endocrine resistance in prostate cancer by enhancing the immunosuppressive microenvironment of these tumors.
Coupling between adhesome assembly and 3D chromatin organization
Item type: Journal Article
Cammarata L.V.; Sengupta D.; Gupta R.; et al. (2026)
Proteins on the cell membrane cluster to respond to extracellular signals; for example, adhesion proteins cluster to enhance extracellular matrix sensing. The maturation of such receptor clusters may require additional adhesome proteins to adapt and reinforce extracellular signal sensing. However, it has been unclear whether the genes encoding these proteins share a spatial organization in the nucleus. Using the adhesome as an example, we show that subsets of genes that code for adhesome proteins exhibit relative spatial clustering and co-regulation in distinct locations within the nucleus. We use Hi-C maps and RNA-seq data from adherent cells to map the correspondence between adhesome gene localization and their expression. Interestingly, we find that the genes encoding several transcription factors, cofactors, and chromatin regulators that regulate these genes are also co-localized with the adhesome gene loci, thereby potentially suggesting a link between the extracellular matrix sensing machinery and gene expression. Additionally, we validate the spatial sub-clustering of adhesome gene loci using MERFISH data and DNA-FISH experiments. Collectively, our results support an association between adhesome gene organization and regulatory state, with a possible role in cellular signal sensing.
An Elastoplastic Constitutive Model for Anisotropic Hydro-Mechanical Response of Opalinus Clay
Item type: Journal Article
Nuus M.; Rinaldi A.P.; Guo G.; et al. (2026)
Opalinus Clay is currently proposed as the host rock for a deep geological repository (DGR) for radioactive waste in Switzerland. Gas is expected to be generated within the repository due to anoxic corrosion of metallic components and the degradation of organic material, and understanding gas migration is therefore critical, as pressure build-up may induce fracturing and potentially compromise the long-term integrity of the repository. One relevant gas transport mechanism is dilatancy-controlled flow, in which localized dilatant pathways can lead to transient increases in permeability, facilitating gas migration and potentially affecting the barrier performance of the host rock. To investigate and simulate such processes, a constitutive model is required that captures hydro-mechanical (HM) behavior, including the influence of bedding-induced anisotropy, yield behavior, and strain-dependent hardening and softening. In this study, consolidated undrained (CU) triaxial tests performed on Opalinus Clay specimens with varying bedding orientations (in increments of (Formula presented.)) are used to calibrate and evaluate the columnar-basalt (COMBA) constitutive model implemented in FLAC3D. The model allows for the explicit representation of bedding through oriented joint sets, enabling orientation-dependent failure criteria, anisotropic stiffness, and strain-dependent evolution of strength parameters. The constitutive model is subsequently applied to a coupled hydro-mechanical simulation of a gas injection experiment conducted at the Mont Terri Rock Laboratory. Comparison with a previously applied ubiquitous-joint formulation shows that the COMBA constitutive model reproduces the observed hydraulic response and deformation localization, while providing a more accurate prediction of the timing of deformation measured by distributed fiber-optic sensing, although the accumulated deformation is overpredicted at later times. The improved representation of bedding anisotropy further provides a clearer insight into the gas migration mechanism, with the close correspondence between plastic shear strain and gas breakthrough supporting shear–slip dilation along the bedding planes as a likely mechanism for pathway formation.
Aerosol–cloud interactions influence the climate response to AMOC weakening
Item type: Journal Article
Vella R.; Lohmann U. (2026)
The Atlantic Meridional Overturning Circulation (AMOC) strongly influences regional climate, yet how atmospheric aerosols and aerosol–cloud interactions respond to its weakening remains largely unexplored. Using an aerosol-climate model, we examine how a 60% AMOC weakening affects aerosols, clouds, and radiation. The weakening drives a hemispheric aerosol redistribution through purely dynamical pathways, increasing the Northern Hemisphere aerosol burden by 41% through enhanced Saharan dust emissions and longer lifetimes under suppressed wet deposition. Averaged over 40–90° N, in-cloud droplet number increases by 10% in warm clouds and 11% in mixed-phase clouds, while enhanced dust ice-nucleating particles raise mixed-phase ice crystal number by 32%, promoting the Wegener–Bergeron–Findeisen process and reducing mixed-phase total water path by 8%. A kernel decomposition shows substantial regional cloud radiative responses, particularly over the North Atlantic, but opposing contributions largely cancel in the global mean, leaving a small net cloud radiative response of +0.21Wm-2. This near cancellation reflects subpolar low-cloud brightening offset by optical thinning of mixed-phase and ice clouds, partly driven by dust-induced glaciation, together with opposing tropical cloud changes from the southward ITCZ shift. This small global mean cloud contribution contrasts with previous studies of AMOC weakening, in which cloud changes contribute a net positive radiative feedback on the surface response. Of the cloud, aerosol and surface-albedo contributions diagnosed here, the largest effect comes from the enhanced shortwave reflection by expanded sea-ice and snow cover (−0.83 W m−2), followed by the effective radiative forcing due to dust aerosol–radiation interactions (ERFari, −0.23 W m−2). Combined with the cloud contribution, these terms sum to −0.86 W m−2. This estimate excludes the longwave response to the cooling, including the Planck and lapse-rate responses, which is not decomposed here.
Benchmarking convection-permitting climate simulations for hydrometeorological characterizations: a comparative study of WRF-SAAG and observation-based products in Chile
Item type: Journal Article
Segovia-Escafi S.; Mendoza P.A.; Lagos-Zúñiga M.; et al. (2026)
Over the last few years, significant progress has been made in the development of convection-permitting climate models (CPCMs), especially in improving precipitation estimates in regions with complex terrain. Recently, the South American Affinity Group (SAAG) developed a novel high-resolution dataset – hereafter referred to as the WRF-SAAG dataset – by dynamically downscaling the ERA5 reanalysis using the Weather Research and Forecasting (WRF) model over South America for the period 2000–2021. Here, we evaluate WRF-SAAG outputs across continental Chile and compare them with two widely used gridded meteorological products, CR2MET and RF-MEP, which combine reanalysis data with in situ measurements. In particular, we analyze spatial differences among climatological estimates from the three products, and we assess the quality of daily precipitation and daily maximum and minimum temperature simulations using observations from meteorological stations over the period April/2001–March/2018. We also compare the potential of these climate datasets for hydrological modeling using a conceptual, bucket-style rainfall-runoff model, evaluating the results against streamflow observations, satellite remote sensing (SRS) products, and a snow water equivalent (SWE) reanalysis product. We found that the detection accuracy varied within each Chilean macrozone, with worse performance in the Far North (17.5–26° S) and Patagonia (43.7–56° S). The evaluation of daily precipitation against station observations using Tang's Kling–Gupta efficiency (KGET) reveals that all datasets performed better in reproducing precipitation in rainy regions (median KGET ≥ 0.65 in the Southern macrozone), while in arid areas such as the Near North during summer, the median KGET was negative. The CR2MET product consistently provided the best performance for extreme precipitation and temperature, partly because it includes information from the stations used for evaluation. Finally, the application of the hydrological model shows that although WRF-SAAG simulations achieved runoff estimations comparable to the best observation-based gridded products (i.e., CR2MET or RF-MEP), with the best results in the southern macrozone they provided relatively lower performance in evapotranspiration (ET) and soil moisture estimates, as well as SWE simulations of competitive quality. More broadly, the results presented here show that, despite some remaining challenges in arid climate regions, kilometer-scale climate models can deliver valuable information for hydrological applications at the daily time scale in Chile.