bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Dimensional Quantitative Comparison of Density Distributions in Detrital Geochronology and Geochemistry
Authors: Sundell K. E. , Saylor J. E.
Published: February 2021

Detrital geochronology provides insight into a broad range of Earth Science questions. However, detrital zircon U‐Pb age distributions are inherently univariate, and thus quantitative comparison methods are limited to one‐dimension (1D) and subject to nonunique results due to overlapping age groups. We developed two‐dimensional (2D) quantitative comparison measures for bivariate kernel density estimates (KDEs) and cumulative distribution functions (CDFs). These methods are extensions of 1D quantitative comparison measures commonly used in detrital geochronology: Similarity, Likeness, and Cross‐correlation of KDEs and Kolmogorov‐Smirnov (K‐S) and Kuiper tests of CDFs. We demonstrate the efficacy of these methods by applying them to a global compilation of detrital and igneous zircon univariate U‐Pb data (n = 767,660) and bivariate U‐Pb and Hf (i.e., εHfT) data (n = 114,311) parsed geographically into eight continental landmasses demarcated by Paleozoic sutures. The 2D quantitative comparison measures behave in a similar fashion to their 1D counterparts in terms of sensitivity and consistency regardless of parameterization (e.g., kernel bandwidth and discretization interval). Results show that the detrital record reliably reflects the igneous record for both univariate U‐Pb and bivariate εHfT distributions between 4,400 and 0 Ma. In contrast, 1D and 2D quantitative comparison results differ over the narrower Ediacaran‐Cambrian time interval due to nonunique univariate zircon U‐Pb age groups; the 2D quantitative results consistently identify continental landmasses involved in the formation of Gondwana. We implemented the 2D methods in a new MATLAB‐based graphical user interface, DZstats2D, which is available as open‐source code and as standalone applications for macOS and Windows.
Atmospheric Transport of North African Dust‐Bearing Supermicron Freshwater Diatoms to South America: Implications for Iron Transport to the Equatorial North Atlantic Ocean
Authors: Barkley Anne E. , Olson Nicole E. , Prospero Joseph M. , Gatineau Alexandre , Panechou Kathy , Maynard Nancy G. , Blackwelder Patricia , China Swarup , Ault Andrew P. , Gaston Cassandra J.
Published: February 2021

The equatorial North Atlantic Ocean (NAO) is a nutrient‐limited ecosystem that relies on the deposition of long‐range transported iron (Fe)‐containing aerosols to stimulate primary productivity. Using microscopy, we characterized supermicron and supercoarse mode African aerosols transported to the western NAO in boreal winter/spring. We detected three particle types including African dust, primary biological aerosol particles, and freshwater diatoms (FDs). FDs contained 4% Fe by weight due to surficial dust inclusions that may be susceptible to chemical processing and dissolution. FDs were typically larger than dust particles and comprised 38% of particles between 10 and 18 μm in diameter. The low density, high surface‐area‐to‐volume ratio, and large aspect ratios of FD particles suggest a mechanism by which they can be carried great distances aloft. These same properties likely increase the residence time of FDs in surface waters thereby increasing the time for Fe dissolution and their potential impact on marine biogeochemical cycles.
Dry Spells, Wet Days, and Their Trends Across Southern Africa During the Summer Rainy Season
Authors: Thoithi Wanjiru , Blamey Ross C. , Reason Chris J. C.
Published: February 2021

Dry spell frequency and wet day occurrence during the summer rainy season across southern Africa are examined using daily rainfall for 1982–2019. Evidence shows two sharp gradients in dry spell frequency, extending southeast from southern Angola to the African south coast near the westernmost boundary of preferred cloud band occurrences (diagonal gradient), and west from the Limpopo River Valley along 22–24°S (meridional gradient) (along 14–16°S in early summer) related to regional topography. Trend analysis suggests that the diagonal gradient has weakened during 1982–2019 along with some other large areas in southern Africa whereas this is only true for part of the meridional gradient. Contrastingly, wet days and Normalized Difference Vegetation Index have significantly increased in several important agricultural areas in southern Africa. Evidence suggests these changes are related to those in the midlevel Botswana High, El Niño Southern Oscillation, Southern Annular Mode, and subtropical Indian Ocean dipole.
Improving Surface Soil Moisture Estimates in Humid Regions by an Enhanced Remote Sensing Technique
Authors: Song Peilin , Zhang Yongqiang , Tian Jing
Published: February 2021

Using optical remote sensing data to downscale microwave soil moisture is currently a crucial technique for producing fine‐resolution soil moisture data set at large scales. Conventional soil moisture downscaling models are mainly developed and evaluated in arid or semi‐arid regions, but have serious limitation in humid regions. To improve soil moisture estimates under a wide range of climate regimes, this study developed a nonlinear enhanced soil moisture downscaling model and evaluated it at a typical microwave resolution over the contiguous China. The enhanced model clearly outperforms the conventional approach in estimating surface soil moisture by reducing the Root Mean Square Error (RMSE) from 0.175 vol/vol to 0.075 vol/vol under wet climate. Finally, soil moisture downscaling is conducted by applying such models (built at the 25‐km scale) at a finer (1‐km) resolution. Validation result of downscaled soil moisture against in situ data set demonstrates the advantage of the enhanced model.
Energetic Electron Precipitation Observed by FIREBIRD‐II Potentially Driven by EMIC Waves: Location, Extent, and Energy Range From a Multievent Analysis
Authors: Capannolo L. , Li W. , Spence H. , Johnson A. T. , Shumko M. , Sample J. , Klumpar D.
Published: February 2021

We evaluate the location, extent, and energy range of electron precipitation driven by ElectroMagnetic Ion Cyclotron (EMIC) waves using coordinated multisatellite observations from near‐equatorial and Low‐Earth‐Orbit (LEO) missions. Electron precipitation was analyzed using the Focused Investigations of Relativistic Electron Burst Intensity, Range and Dynamics (FIREBIRD‐II) CubeSats, in conjunction either with typical EMIC‐driven precipitation signatures observed by Polar Orbiting Environmental Satellites (POES) or with in situ EMIC wave observations from Van Allen Probes. The multievent analysis shows that electron precipitation occurred in a broad region near dusk (16–23 MLT), mostly confined to 3.5–7.5 L‐shells. Each precipitation event occurred on localized radial scales, on average ∼0.3 L. Most importantly, FIREBIRD‐II recorded electron precipitation from ∼200 to 300 keV to the expected ∼MeV energies for most cases, suggesting that EMIC waves can efficiently scatter a wide energy range of electrons.
Aquifer Monitoring Using Ambient Seismic Noise Recorded With Distributed Acoustic Sensing (DAS) Deployed on Dark Fiber
Authors: Rodríguez Tribaldos Verónica , Ajo‐Franklin Jonathan B.
Published: February 2021

Groundwater is a critical resource for human activities worldwide, and a vital component of many natural ecosystems. However, the state and dynamics of water‐bearing aquifers remain uncertain, mostly due to the paucity of subsurface data at high spatial and temporal resolution. Here, we show that analysis of infrastructure‐generated ambient seismic noise acquired on distributed acoustic sensing (DAS) arrays has potential as a tool to track variations in seismic velocities (dv/v) caused by groundwater level fluctuations. We analyze 5 months of ambient noise acquired along an unused, 23 km‐long telecommunication fiber‐optic cable in the Sacramento Valley, CA, a so‐called “dark fiber." Three array subsections, ∼6 km apart, are processed and the stretching technique is applied to retrieve daily dv/v beneath each location. Near the Sacramento river, dv/v variations in the order of 2%–3% correlate with precipitation events and fluctuations in river stage of ∼1.5 m. In contrast, regions away (2.5 km) from the river do not experience large dv/v variations. These observations reveal short‐scale spatial variability in aquifer dynamics captured by this approach. Dispersion analysis and surface wave inversion of noise gathers reveal that seismic velocity perturbations occur at depths of 10–30 m. Rock physics modeling confirms that observed dv/v are linked to pore pressure changes at these depths, caused by groundwater table fluctuations. Our results suggest that DAS combined with ambient noise interferometry provides a means of tracking aquifer dynamics at high spatial and temporal resolutions at local to regional scales, relevant for effective groundwater resource management.
Mapping Stress and Fluids on Faults by Nonshear Earthquakes
Authors: Vavryčuk Václav , Adamová Petra , Doubravová Jana , Ren Yi
Published: February 2021

Fluids on faults facilitate triggering of earthquakes and affect seismic energy release. Their detection in the focal zone is, however, difficult. Here, we present mapping of stress changes and fluid flow based on determining seismic moment tensors (MTs), which describe focal mechanisms and shear/tensile/compressive fracturing modes of earthquake sources. We calculate highly accurate MTs of 4,500 microearthquakes that occurred in the West Bohemia swarm region in the period of 2008–2018. The extent and quality of the moment tensor data are unique and allow us to study detailed behavior of the nondouble‐couple (nonDC) components of MTs along the fault. The nonDC components were mostly zero or negative and indicated shear/compressive fracturing. However, also a patch with positive nonDC components, indicating tensile fracturing, was revealed. The inversion for stress and modeling of the Coulomb stress change confirmed that this patch is under anomalous stress conditions. Tensile fractures in the patch were opened due to interaction of tensile fault steps and filled by overpressurized fluids. Hence, evaluating nonDC components of earthquakes might help for tracing stress variations and fault interactions, identifying pathways of fluids and locating areas with overpressure prone to being activated.
Emergent Properties of Convection in OTREC and PREDICT
Authors: Raymond D. J. , Fuchs‐Stone Ž.
Published: February 2021

Data from recent field programs studying deep convection may be useful in constraining cumulus parameterizations. To this end, gridded dropsonde analyses are made using data from the OTREC (Organization of Tropical East Pacific Convection) and PREDICT (PreDepression Investigation of Cloud‐Systems in the Tropics) projects to characterize the mesoscale properties of tropical oceanic convection in terms of selected thermodynamic parameters computable from the explicit grids of large‐scale models. In particular, saturation fraction, lower tropospheric moist convective instability, and convective inhibition appear to govern column‐integrated moisture convergence, while sea surface temperature is related to the top‐heaviness of mass flux profiles and the integrated entropy divergence. Local (as opposed to global) surface heat and moisture fluxes and convective available potential energy correlate weakly with these quantities. Recommendations to improve cumulus parameterizations are enumerated.
Influence of African Atmospheric Rivers on Precipitation and Snowmelt in the Near East's Highlands
Authors: Bozkurt D. , Sen O. L. , Ezber Y. , Guan B. , Viale M. , Caglar F.
Published: February 2021

Atmospheric rivers (ARs) traveling thousands of kilometers over arid North Africa could interact with the highlands of the Near East (NE), and thus affect the region's hydrometeorology and water resources. Here, we use a state‐of‐the‐art AR tracking database, and reanalysis and observational datasets to investigate the climatology (1979–2017) and influences of these ARs in snowmelt season (March–April). The Red Sea and northeast Africa are found to be the major source regions of these ARs, which are typically associated with the eastern Mediterranean trough positioned over the Balkan Peninsula and a blocking anticyclone over the NE‐Caspian region, triggering southwesterly air flow toward the NE's highlands. Approximately 8% of the ARs are relatively strong (integrated water vapor transport >∼275 kg m−1 s−1). AR days exhibit enhanced precipitation over the crescent‐shaped orography of the NE region. Mean AR days indicate wetter (up to + 2 mm day−1) and warmer (up to + 1.5°C) conditions than all‐day climatology. On AR days, while snowpack tends to decrease (up to 30%) in the Zagros Mountains, it can show decreases or increases in the Taurus Mountains depending largely on elevation. A further analysis with the observations and reanalysis indicates that extreme ARs coinciding with large scale sensible heat transport can significantly increase the daily discharges. These results suggest that ARs can have notable impacts on the hydrometeorology and water resources of the region, particularly of lowland Mesopotamia, a region that is famous with great floods in the ancient narratives.
Interpreting the Diurnal Cycle of Clouds and Precipitation in the ARM GoAmazon Observations: Shallow to Deep Convection Transition
Authors: Tian Yang , Zhang Yunyan , Klein Stephen A. , Schumacher Courtney
Published: February 2021

The Green Ocean Amazon (GoAmazon) 2014/5 field campaign data are used to study the diurnal cycle of clouds and precipitation. Through a careful classification of days with shallow cumulus, congestus and deep convection, we investigate the major differences among locally generated convection regimes and the most important environmental factors governing the shallow‐to‐deep convection transition. On shallow cumulus days, a greater sensible heat flux drives deeper boundary layer growth, which entrains drier free‐tropospheric air and lowers the relative humidity, thus leading to a significantly higher cloud base than those on days with deeper convection. Congestus and deep convection regimes exhibit distinct cloud top height distributions with noticeable differences in the vertical wind shear in the mid‐troposphere, suggesting an important role of wind shear in limiting the vertical extent of convection. On deep convection days, with preexisting nocturnal convection or cold‐pools from external disturbances, the timing of peak surface precipitation (12:00–13:00 LST) tends to be in‐phase with the diurnal variation in surface fluxes. However, it takes longer for local deep convection to develop without these disturbances. A plume model with thermodynamic and dynamical constraints is developed to explore the relative importance of various convection‐controlling factors. Initial cloud‐base vertical velocity and buoyancy are important in helping parcels ascend to the level of free convection (LFC). After parcels reach the LFC, entrainment of environmental air and lower free troposphere humidity become crucial in determining cloud top. Entrainment rate differentiates among convection regimes, which may be tied to the cloud size distribution at cloud base.
Impact of Urban Roughness Representation on Regional Hydrometeorology: An Idealized Study
Authors: Li Qi , Yang Jiachuan , Yang Long
Published: February 2021

Mesoscale climate models provide indispensable tools to understand land‐atmosphere interactions over urban regions. However, uncertainties in urban canopy parameters (UCPs) and parameterization schemes lead to degraded representation of the drag effect in complex built terrains. In particular, for the widely applied single‐layer urban canopy model (SLUCM) coupled with the Weather Research and Forecasting (WRF) model, near‐surface horizontal wind speed is known to be overestimated systematically. In this study, idealized large eddy simulations (LES) and WRF‐SLUCM simulations are conducted to study the separate effect of UCPs and aerodynamic parameterization on atmospheric boundary layer processes and rainfall variabilities in Phoenix, Arizona. For LES that explicitly resolves surface geometry, significant differences between three‐dimensional (3D) versus two‐dimensional (2D) representation of urban morphology are found in the surface layer and above. When surface drag is parameterized following SLUCM, surface morphologies have little impacts on the mean momentum transfer. WRF‐SLUCM simulation results, incorporated with 3D urban morphology data, indicate that simply refining the frontal area index will reduce the surface drag, which further amplifies the systematic positive bias of SLUCM in predicting horizontal wind speed. Replacing the drag parameterization in SLUCM by LES‐based aerodynamic parameters has evident impacts on near‐surface wind speed. The impact of urban roughness representation becomes the most evident during rainfall periods, due to the important role of surface drag in dictating moisture convergence. Our study underlines that apart from intensive efforts in obtaining detailed UCPs, it is also critical to enhance the urban momentum exchange parameterization schemes.
Characteristics of Propagation From Meteorological Drought to Hydrological Drought in the Pearl River Basin
Authors: Zhou Zhaoqiang , Shi Haiyun , Fu Qiang , Ding Yibo , Li Tianxiao , Wang Yao , Liu Suning
Published: February 2021

Drought events occur more frequently under recent climate change. Generally, meteorological drought is the fuse of hydrological drought; thus, it is important to understand the characteristics of meteorological drought and its propagation to hydrological drought for early warning. Taking the Pearl River Basin (PRB) in China as study area, this study adopted K‐means cluster analysis method to divide the PRB into subregions with similar precipitation characteristics. Then, standardized precipitation index and standardized runoff index were used to analyze the characteristics of meteorological drought and hydrological drought, respectively, and the maximum Pearson correlation coefficient was used to determine the drought propagation time (DPT) between these two types of drought. Moreover, the link between meteorological drought and hydrological drought was explored based on continuous wavelet transform and cross wavelet transform. The results revealed that: the PRB has experienced severe meteorological and hydrological droughts since early 2000s, and hydrological drought was more serious than meteorological drought in each of the five subregions in the PRB. The DPTs from meteorological drought to hydrological drought were mainly 2–6 months, and the periodic characteristics of meteorological drought were mainly responsible for those of hydrological drought. Precipitation and runoff could greatly affect the DPT, while the impacts of evapotranspiration and shallow soil moisture on the DPT were not significant. Furthermore, El‐Niño Southern Oscillation and Pacific Decadal Oscillation are important factors that affect the DPT from meteorological to hydrological drought in the PRB.
The Aeolian Environment of the Landing Site for the ExoMars Rosalind Franklin Rover in Oxia Planum, Mars
Authors: Favaro E. A. , Balme M. R. , Davis J. M. , Grindrod P. M. , Fawdon P. , Barrett A. M. , Lewis S. R.
Published: February 2021

Aeolian features at Oxia Planum—the 2023 landing site for the ExoMars Rosalind Franklin Rover (ERFR)—are important for Mars exploration because they record information about past and current wind regimes, sand transport vectors, and lend insight to the abrasion, deposition, and transport of granular material. To characterize the wind regime and erosional history of Oxia Planum we used a combination of manual observational and machine‐learning techniques to analyze the morphometrics, distribution, and orientation of 10,753 aeolian bedforms (Transverse Aeolian Ridges[TARs]) and landforms (Periodic Bedrock Ridges [PBRs]) around the ERFR landing ellipses. We found that, irrespective of the scale of the TARs, crestline azimuths are consistent across the study area and we infer that the bedform forming winds blew from NW‐NNW toward SE‐SSE. PBR azimuths show a substantively different orientation to the aeolian bedforms, and we infer that the winds necessary to abrade PBRs had a N‐NNE or S‐SSE orientation (180° ambiguity). From observations of active dust devils and windstreaks from repeat imagery, we infer a W‐WNW or E‐ESE (180° ambiguity) wind dominates today. Finally, we compare the inferred wind direction results from the aeolian landscape to modeled wind data from Mars Global Circulation Models. We note that, despite landscape evidence to the contrary, modeled contemporary wind direction lacks the consistent directionality to be responsible for the orientation of aeolian features in Oxia Planum. These results characterize aeolian features ERFR will encounter and suggests multiple wind regimes have influenced the surficial expression of the landing site.
Distributions of Ion Density Irregularities and Their Gradients Inside Low‐Latitude Ionospheric Plasma Bubbles Based on C/NOFS Planar Langmuir Probe Data
Authors: Costa Emanoel , Roddy Patrick A. , Ballenthin John O.
Published: February 2021

Data from the planar Langmuir probe onboard the Communication/Navigation Outage Forecasting System has been processed, with focus on the: (1) identification of Equatorial Plasma Bubbles located within the eclipse sections of the satellite orbits; (2) subdivision of each Equatorial Plasma Bubble into three sections (West Wall, Center, and East Wall); and (3) statistical analyses of the standard deviations and gradients of ion density data for each section. The statistical distributions resulted from the application of the above processing to structures identified during the years October 1, 2008 to September 30, 2009 (solar minimum conditions) and June 5, 2012 to June 4, 2013 (close to maximum conditions of solar cycle 24). The statistical distributions have also been classified considering all longitudes or three 60° longitude sectors in South America, Africa, India‐Asia, as well as all altitudes of the C/NOFS satellite or the limited range from 650 to 800 km. It will be shown that all the parameters (Equatorial Plasma Bubble sections, solar activity, longitude sector, and altitude range) affect the resulting statistical distributions. Additionally, the probability density functions (pdfs) of ion density gradients for the EPB West Walls, Centers, and East Walls and the South American longitude sector, detected during 2012 and estimated with different resolutions will be compared. While the pdfs based on 1‐Hz low‐resolution data (sampling large‐scale structures) display east‐west asymmetries, those based on the original 512‐Hz high‐resolution data (sampling small‐scale structures), created by secondary plasma instabilities, are essentially symmetric around the reference 0 mm/km gradient.
MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer
Authors: Pan Jhih-Kai , Lin Cheng-Han , Kuo Yao-Lung , Ger Luo-Ping , Cheng Hui-Chuan , Yao Yun-Chin , Hsiao Michael , Lu Pei-Jung
Published: February 2021

Brian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.
Prognostic significance of esterase gene expression in multiple myeloma
Authors: Kumari Romika , Majumder Muntasir Mamun , Lievonen Juha , Silvennoinen Raija , Anttila Pekka , Nupponen Nina N. , Lehmann Fredrik , Heckman Caroline A.
Published: February 2021

Background

Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM).

Methods

For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM.

Results

MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis.

Conclusions

Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.
Modulation of intratumoural myeloid cells, the hallmark of the anti-tumour efficacy induced by a triple combination: tumour-associated peptide, TLR-3 ligand and α-PD-1
Authors: Zalba Sara , Belsúe Virginia , Topp Brian , de Alwis Dinesh , Alvarez Maite , Trocóniz Iñaki F. , Berraondo Pedro , Garrido María J.
Published: February 2021

Background

Anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monoclonal antibodies (mAbs) show remarkable clinical anti-tumour efficacy. However, rational combinations are needed to extend the clinical benefit to primary resistant tumours. The design of such combinations requires the identification of the kinetics of critical immune cell populations in the tumour microenvironment.

Methods

In this study, we compared the kinetics of immune cells in the tumour microenvironment upon treatment with immunotherapy combinations with different anti-tumour efficacies in the non-inflamed tumour model TC-1/A9. Tumour-bearing C57BL/6J mice were treated with all possible combinations of a human papillomavirus (HPV) E7 long peptide, polyinosinic–polycytidylic acid (PIC) and anti-PD-1 mAb. Tumour growth and kinetics of the relevant immune cell populations were assessed over time. The involvement of key immune cells was confirmed by depletion with mAbs and immunophenotyping with multiparametric flow cytometry.

Results

The maximum anti-tumour efficacy was achieved after intratumoural administration of HPV E7 long peptide and PIC combined with the systemic administration of anti-PD-1 mAb. The intratumoural immune cell kinetics of this combination was characterised by a biphasic immune response. An initial upsurge of proinflammatory myeloid cells led to a further rise in effector CD8+ T lymphocytes at day 8. Depletion of either myeloid cells or CD8+ T lymphocytes diminished the anti-tumour efficacy of the combination.

Conclusions

The anti-tumour efficacy of a successful immunotherapy combination in a non-inflamed tumour model relies on an early inflammatory process that remodels the myeloid cell compartment.
Correction: Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study
Authors: Hajiev Saur , Allara Elias , Motedayеn Aval Leila , Arizumi Tadaaki , Bettinger Dominik , Pirisi Mario , Rimassa Lorenza , Pressiani Tiziana , Personeni Nicola , Giordano Laura , Kudo Masatoshi , Thimme Robert , Park Joong-Won , Taddei Tamar H. , Kaplan David E. , Ramaswami Ramya , Pinato David J. , Sharma Rohini
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41416-020-01241-5
More light on cancer and COVID-19 reciprocal interaction
Authors: Brest Patrick , Mograbi Baharia , Hofman Paul , Milano Gerard
Published: February 2021

Cancer patients are vulnerable to COVID-19 with consequences on treatment delays and on mortality rate. This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and TMPRSS2, the proteases which control ACE2 processing, the SARS-CoV-2 target.
The bovine dialysable leukocyte extract IMMUNEPOTENT CRP induces immunogenic cell death in breast cancer cells leading to long-term antitumour memory
Authors: Reyes-Ruiz Alejandra , Calvillo-Rodriguez Kenny Misael , Martínez-Torres Ana Carolina , Rodríguez-Padilla Cristina
Published: February 2021

Background

Cancer recurrence is a serious problem in breast cancer (BC) patients, and immunogenic cell death (ICD) has been proposed as a strategy to overcome this recurrence. IMMUNEPOTENT CRP (ICRP) acts as an immunomodulator and can be cytotoxic to cancer cells. Thus, we evaluated if ICRP induces ICD in BC cells.

Methods

Immunogenicity of ICRP-induced cell death was evaluated in vitro, analysing the principal biochemical characteristics of ICD in MCF-7, MDA-MB-231 and 4T1 cells. Ex vivo, we assessed the ability of killed cancer cells (KCC) obtained from ICRP-treated 4T1 cells (ICRP-KCC) to induce DC maturation, T-cell priming and T-cell-mediated cancer cytotoxicity. In vivo, we evaluated tumour establishment and antitumour immune memory after prophylactic ICRP-KCC vaccination in BALB/c mice.

Results

ICRP induced caspase-independent, ROS-dependent cell death, autophagosome formation, P-eIF2α, chaperone protein exposure, CD47 loss, ATP and HMBG1 release in BC cells. Additionally, ICRP-KCC promoted DC maturation, which triggered T-cell priming and cancer cytotoxicity. Prophylactic vaccination with ICRP-KCC prevented tumour establishment and induced long-term antitumour memory in BALB/c mice, involving DC maturation in lymph nodes, CD8+ T-cell augmentation in lymph nodes, peripheral blood and tumour site and ex vivo tumour-specific cytotoxicity by splenocytes.

Conclusions

ICRP induces ICD in BC cells, leading to long-term antitumour memory.
Hepatic metastasis of gastric cancer is associated with enhanced expression of ethanolamine kinase 2 via the p53–Bcl-2 intrinsic apoptosis pathway
Authors: Miwa Takashi , Kanda Mitsuro , Shimizu Dai , Umeda Shinichi , Sawaki Koichi , Tanaka Haruyoshi , Tanaka Chie , Hattori Norifumi , Hayashi Masamichi , Yamada Suguru , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro
Published: February 2021

Background

Gastric cancer (GC) with hepatic metastasis has a poor prognosis. Understanding the molecular mechanisms involved in hepatic metastasis may contribute to the development of sensitive diagnostic biomarkers and novel therapeutic strategies.

Methods

We performed transcriptome analysis of surgically resected specimens from patients with advanced GC. One of the genes identified as specifically associated with hepatic metastasis was selected for detailed analysis. GC cell lines with knockout of the candidate gene were evaluated in vitro and in vivo. Expression of the candidate gene was analysed in GC tissues from 300 patients.

Results

Ethanolamine kinase 2 (ETNK2) was differentially upregulated in GC patients with hepatic metastasis. ETNK2 expression was elevated in GC cell lines derived from haematogenous metastases. ETNK2 knockout significantly suppressed proliferation, invasion, and migration; increased apoptosis; reduced Bcl-2 protein expression; and increased phosphorylated p53 expression. In mouse xenograft models, ETNK2 knockout virtually abolished hepatic metastasis. Stratification of GC patients based on ETNK2 mRNA level revealed significant associations between high ETNK2 tumour expression and both hepatic recurrence and worse prognosis.

Conclusions

Upregulation of ETNK2 in GC enhances hepatic metastasis, possibly via dysregulation of p53–Bcl-2-associated apoptosis. ETNK2 expression may serve as a biomarker for predicting hepatic recurrence and a therapeutic target.
Novel STAR gene variant in a patient with classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency
Authors: Higa Moritake , Zaha Akiko , Takushi Akiko , Morishima Nami , Majikina Toyofumi , Touma Takeshi , Shimabukuro Michio , Masuzaki Hiroaki , Honda Misa , Hasegawa Tomonobu
Published: February 2021

We report the first case of classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency. We identified pathogenic variants in the STAR gene: a novel variant of c.126_127delCCinsG, namely, p.Thr44Profs*2 and an already reported variant of c.634C>T, namely, p.Gln212*. The association with combined pituitary hormone deficiency might be just a coincidence.
A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits
Authors: Foley Christopher N. , Staley James R. , Breen Philip G. , Sun Benjamin B. , Kirk Paul D. W. , Burgess Stephen , Howson Joanna M. M.
Published: February 2021

Genome-wide association studies (GWAS) have identified thousands of genomic regions affecting complex diseases. The next challenge is to elucidate the causal genes and mechanisms involved. One approach is to use statistical colocalization to assess shared genetic aetiology across multiple related traits (e.g. molecular traits, metabolic pathways and complex diseases) to identify causal pathways, prioritize causal variants and evaluate pleiotropy. We propose HyPrColoc (Hypothesis Prioritisation for multi-trait Colocalization), an efficient deterministic Bayesian algorithm using GWAS summary statistics that can detect colocalization across vast numbers of traits simultaneously (e.g. 100 traits can be jointly analysed in around 1 s). We perform a genome-wide multi-trait colocalization analysis of coronary heart disease (CHD) and fourteen related traits, identifying 43 regions in which CHD colocalized with ≥1 trait, including 5 previously unknown CHD loci. Across the 43 loci, we further integrate gene and protein expression quantitative trait loci to identify candidate causal genes.
Simulating the ghost: quantum dynamics of the solvated electron
Authors: Lan Jinggang , Kapil Venkat , Gasparotto Piero , Ceriotti Michele , Iannuzzi Marcella , Rybkin Vladimir V.
Published: February 2021

The nature of the bulk hydrated electron has been a challenge for both experiment and theory due to its short lifetime and high reactivity, and the need for a high-level of electronic structure theory to achieve predictive accuracy. The lack of a classical atomistic structural formula makes it exceedingly difficult to model the solvated electron using conventional empirical force fields, which describe the system in terms of interactions between point particles associated with atomic nuclei. Here we overcome this problem using a machine-learning model, that is sufficiently flexible to describe the effect of the excess electron on the structure of the surrounding water, without including the electron in the model explicitly. The resulting potential is not only able to reproduce the stable cavity structure but also recovers the correct localization dynamics that follow the injection of an electron in neat water. The machine learning model achieves the accuracy of the state-of-the-art correlated wave function method it is trained on. It is sufficiently inexpensive to afford a full quantum statistical and dynamical description and allows us to achieve accurate determination of the structure, diffusion mechanisms, and vibrational spectroscopy of the solvated electron.
Laboratory disruption of scaled astrophysical outflows by a misaligned magnetic field
Authors: Revet G. , Khiar B. , Filippov E. , Argiroffi C. , Béard J. , Bonito R. , Cerchez M. , Chen S. N. , Gangolf T. , Higginson D. P. , Mignone A. , Olmi B. , Ouillé M. , Ryazantsev S. N. , Skobelev I. Yu. , Safronova M. I. , Starodubtsev M. , Vinci T. , Willi O. , Pikuz S. , Orlando S. , Ciardi A. , Fuchs J.
Published: February 2021

The shaping of astrophysical outflows into bright, dense, and collimated jets due to magnetic pressure is here investigated using laboratory experiments. Here we look at the impact on jet collimation of a misalignment between the outflow, as it stems from the source, and the magnetic field. For small misalignments, a magnetic nozzle forms and redirects the outflow in a collimated jet. For growing misalignments, this nozzle becomes increasingly asymmetric, disrupting jet formation. Our results thus suggest outflow/magnetic field misalignment to be a plausible key process regulating jet collimation in a variety of objects from our Sun’s outflows to extragalatic jets. Furthermore, they provide a possible interpretation for the observed structuring of astrophysical jets. Jet modulation could be interpreted as the signature of changes over time in the outflow/ambient field angle, and the change in the direction of the jet could be the signature of changes in the direction of the ambient field.
Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury
Authors: Brommer Benedikt , He Miao , Zhang Zicong , Yang Zhiyun , Page Jessica C. , Su Junfeng , Zhang Yu , Zhu Junjie , Gouy Emilia , Tang Jing , Williams Philip , Dai Wei , Wang Qi , Solinsky Ryan , Chen Bo , He Zhigang
Published: February 2021

After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.
Imaging non-collinear antiferromagnetic textures via single spin relaxometry
Authors: Finco Aurore , Haykal Angela , Tanos Rana , Fabre Florentin , Chouaieb Saddem , Akhtar Waseem , Robert-Philip Isabelle , Legrand William , Ajejas Fernando , Bouzehouane Karim , Reyren Nicolas , Devolder Thibaut , Adam Jean-Paul , Kim Joo-Von , Cros Vincent , Jacques Vincent
Published: February 2021

Antiferromagnetic materials are promising platforms for next-generation spintronics owing to their fast dynamics and high robustness against parasitic magnetic fields. However, nanoscale imaging of the magnetic order in such materials with zero net magnetization remains a major experimental challenge. Here we show that non-collinear antiferromagnetic spin textures can be imaged by probing the magnetic noise they locally produce via thermal populations of magnons. To this end, we perform nanoscale, all-optical relaxometry with a scanning quantum sensor based on a single nitrogen-vacancy (NV) defect in diamond. Magnetic noise is detected through an increase of the spin relaxation rate of the NV defect, which results in an overall reduction of its photoluminescence signal under continuous laser illumination. As a proof-of-concept, the efficiency of the method is demonstrated by imaging various spin textures in synthetic antiferromagnets, including domain walls, spin spirals and antiferromagnetic skyrmions. This imaging procedure could be extended to a large class of intrinsic antiferromagnets and opens up new opportunities for studying the physics of localized spin wave modes for magnonics.
Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies
Authors: Wan Guijun , Hayden Ashley N. , Iiams Samantha E. , Merlin Christine
Published: February 2021

Many animals use the Earth’s geomagnetic field for orientation and navigation. Yet, the molecular and cellular underpinnings of the magnetic sense remain largely unknown. A biophysical model proposed that magnetoreception can be achieved through quantum effects of magnetically-sensitive radical pairs formed by the photoexcitation of cryptochrome (CRY) proteins. Studies in Drosophila are the only ones to date to have provided compelling evidence for the ultraviolet (UV)-A/blue light-sensitive type 1 CRY (CRY1) involvement in animal magnetoreception, and surprisingly extended this discovery to the light-insensitive mammalian-like type 2 CRYs (CRY2s) of both monarchs and humans. Here, we show that monarchs respond to a reversal of the inclination of the Earth’s magnetic field in an UV-A/blue light and CRY1, but not CRY2, dependent manner. We further demonstrate that both antennae and eyes, which express CRY1, are magnetosensory organs. Our work argues that only light-sensitive CRYs function in animal light-dependent inclination-based magnetic sensing.
Ferroelectric columnar assemblies from the bowl-to-bowl inversion of aromatic cores
Authors: Furukawa Shunsuke , Wu Jianyun , Koyama Masaya , Hayashi Keisuke , Hoshino Norihisa , Takeda Takashi , Suzuki Yasutaka , Kawamata Jun , Saito Masaichi , Akutagawa Tomoyuki
Published: February 2021

Organic ferroelectrics, in which the constituent molecules retain remanent polarization, represent an important topic in condensed-matter science, and their attractive properties, which include lightness, flexibility, and non-toxicity, are of potential use in state-of-the-art ferroelectric devices. However, the mechanisms for the generation of ferroelectricity in such organic compounds remain limited to a few representative concepts, which has hitherto severely hampered progress in this area. Here, we demonstrate that a bowl-to-bowl inversion of a relatively small organic molecule with a bowl-shaped π-aromatic core generates ferroelectric dipole relaxation. The present results thus reveal an unprecedented concept to produce ferroelectricity in small organic molecules, which can be expected to strongly impact materials science.
Conserved strategies of RNA polymerase I hibernation and activation
Authors: Heiss Florian B. , Daiß Julia L. , Becker Philipp , Engel Christoph
Published: February 2021

RNA polymerase (Pol) I transcribes the ribosomal RNA precursor in all eukaryotes. The mechanisms ‘activation by cleft contraction’ and ‘hibernation by dimerization’ are unique to the regulation of this enzyme, but structure-function analysis is limited to baker’s yeast. To understand whether regulation by such strategies is specific to this model organism or conserved among species, we solve three cryo-EM structures of Pol I fromSchizosaccharomyces pombein different functional states. Comparative analysis of structural models derived from high-resolution reconstructions shows that activation is accomplished by a conserved contraction of the active center cleft. In contrast to current beliefs, we find that dimerization of theS. pombepolymerase is also possible. This dimerization is achieved independent of the ‘connector’ domain but relies on two previously undescribed interfaces. Our analyses highlight the divergent nature of Pol I transcription systems from their counterparts and suggest conservation of regulatory mechanisms among organisms.
A scaffold lncRNA shapes the mitosis to meiosis switch
Authors: Andric Vedrana , Nevers Alicia , Hazra Ditipriya , Auxilien Sylvie , Menant Alexandra , Graille Marc , Palancade Benoit , Rougemaille Mathieu
Published: February 2021

Long non-coding RNAs (lncRNAs) contribute to the regulation of gene expression in response to intra- or extracellular signals but the underlying molecular mechanisms remain largely unexplored. Here, we identify an uncharacterized lncRNA as a central player in shaping the meiotic gene expression program in fission yeast. We report that this regulatory RNA, termed mamRNA, scaffolds the antagonistic RNA-binding proteins Mmi1 and Mei2 to ensure their reciprocal inhibition and fine tune meiotic mRNA degradation during mitotic growth. Mechanistically, mamRNA allows Mmi1 to target Mei2 for ubiquitin-mediated downregulation, and conversely enables accumulating Mei2 to impede Mmi1 activity, thereby reinforcing the mitosis to meiosis switch. These regulations also occur within a unique Mmi1-containing nuclear body, positioning mamRNA as a spatially-confined sensor of Mei2 levels. Our results thus provide a mechanistic basis for the mutual control of gametogenesis effectors and further expand our vision of the regulatory potential of lncRNAs.
CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
Authors: Tallón de Lara Paulino , Castañón Héctor , Vermeer Marijne , Núñez Nicolás , Silina Karina , Sobottka Bettina , Urdinez Joaquín , Cecconi Virginia , Yagita Hideo , Movahedian Attar Farkhondeh , Hiltbrunner Stefanie , Glarner Isabelle , Moch Holger , Tugues Sònia , Becher Burkhard , van den Broek Maries
Published: February 2021

Some breast tumors metastasize aggressively whereas others remain dormant for years. The mechanism governing metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identify a discrete population of CD39+PD-1+CD8+T cells in primary tumors and in dormant metastasis, which is hardly found in aggressively metastasizing tumors. Using blocking antibodies, we find that dormancy depends on TNFα and IFNγ. Immunotherapy reduces the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+T cells prevents metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+but not total CD8+T cells correlates with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+T cells for controlling experimental and human breast cancer. Thus, we suggest that a primary breast tumor could prime a systemic, CD39+PD-1+CD8+T cell response that favors metastatic dormancy in the lungs.