bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Climate Changes in the Westernmost Mediterranean (Alboran Sea) Over the Last 35 kyr: New Insights From Four Lipid Paleothermometers (UK'37, TEXH86, RI‐OH', and LDI)
Authors: Morcillo‐Montalbá L. , Rodrigo‐Gámiz M. , Martínez‐Ruiz F. , Ortega‐Huertas M. , Schouten S. , Sinninghe Damsté J. S.
Published: November 2021

The westernmost Mediterranean is one of the most sensitive areas to global climate change and high sedimentation rates allow recording high frequency variability. We present a high‐resolution paleotemperature reconstruction over the last 35 kyr using, for the first time, four independent organic sea surface temperature (SST) proxies (UK'37, TEXH86, RI‐OH' and LDI) based on alkenones, (hydroxy) isoprenoid GDGTs, and long‐chain diols. We also generated a δ18O of planktonic foraminifera G. bulloides record together with records of bulk parameters (total organic carbon content, δ13Corg) and the accumulation rates of different biomarkers to provide insights into terrestrial input and primary producers. All derived‐SST records showed similar trends over the last 35 kyr, revealing abrupt temperature variations during the last seven Dansgaard‐Oeschger (D/O) cycles, the three Heinrich (H) events, the Last Glacial Maximum, and the Younger Dryas. H3 is recognized as the coldest event, while H1 was recorded by all SST proxies as the most abrupt one. In general, TEXH86‐, RI‐OH'‐ and LDI‐SST estimates were lower than those obtained from UK'37. The LDI paleothermometer recorded the largest range of absolute SSTs over the whole period (ca. 20°C) followed by RI‐OH' (ca. 16°C). TEXH86, RI‐OH' and LDI proxies reflected sudden SST changes during the D/O 6 and 5 particularly well. Low BIT values and the abundance of C32 1,15‐diol in range with typical marine values indicated only minor input of continental organic matter. Accumulation rates of different lipid biomarkers were generally modulated by D/O cycles, suggesting enhanced productivity during D/O interstadials and the Bölling‐Alleröd period.
Anomalous Noble Gas Solubility in Liquid Cloud Water: Possible Implications for Noble Gas Temperatures and Cloud Physics
Authors: Hall Chris M. , Castro M. Clara , Scholl Martha A. , Amalberti Julien , Gingerich Stephen B.
Published: November 2021

The noble gas temperature climate proxy is an established tool that has previously been applied to determine the source of groundwater recharge, however, unanswered questions remain. In fractured media (e.g., volcanic islands) recharge can be so rapid that groundwater is significantly depleted in heavy noble gases, indicating that the water has retained noble gas concentrations from higher elevations. Previous studies of rain samples have confirmed a match to patterns seen in fractured‐rock groundwater for heavy noble gases along with a significant helium excess. Snow has been shown to be a credible source for both the helium excess and the observed heavy noble gas pattern. Here, liquid cloud water samples were collected at two mountainous sites and analyzed for noble gas concentrations. A pattern like that of rainwater was found. However, an analysis of diffusive uptake of noble gases into cloud water demonstrates that droplets of 1 mm diameter and smaller should be in constant solubility equilibrium with the atmosphere. To explain this, we present a novel hypothesis that relies on the assumption that liquid water consists of two types of water molecule clusters bounded by hydrogen bonds: a low‐density ice‐like structure and a high‐density condensed structure. In this model, the pressure gradient near the surface of a droplet resulting from surface tension could allow for the formation of a surface layer that is rich in ice‐like low density clusters. This can explain both the helium excess and the heavy noble gas depletion seen in the samples.
Provenance Shifts During Neogene Brahmaputra Delta Progradation Tied to Coupled Climate and Tectonic Change in the Eastern Himalaya
Authors: Betka Paul M. , Thomson Stuart N. , Sincavage Ryan , Zoramthara C. , Lalremruatfela C. , Lang Karl A. , Steckler Michael S. , Bezbaruah Devojit , Borgohain Pradip , Seeber Leonardo
Published: November 2021

The Bengal Basin preserves the erosional signals of coupled tectonic‐climatic change during late Cenozoic development of the Himalayan orogen, yet regional correlation and interpretation of these signals remains incomplete. We present a new geologic map of fluvial‐deltaic deposits of the Indo‐Burman Ranges (IBR), five detrital zircon fission track analyses, and twelve high‐n detrital zircon U‐Pb age distributions (dzUPb) from the Barail (late Eocene–early Miocene), Surma (early–late Miocene), and Tipam (late Miocene–Pliocene) Groups of the ancestral Brahmaputra delta. We use dzUPb statistical tests to correlate the IBR units with equivalent age strata throughout the Bengal Basin. An influx of trans‐Himalayan sediment and the first appearance of ∼50 Ma grains of the Gangdese batholith in the lower Surma Group (∼18–15 Ma) records the early Miocene arrival of the ancestral Brahmaputra delta to the Bengal Basin. Contributions from Himalayan sources systematically decrease up section through the late Miocene as the contribution of Trans‐Himalayan Arc sources increases. The Miocene (∼18–8 Ma) deposition of the Surma Group records upstream expansion of the ancestral Brahmaputra River into southeastern Tibet. Late Miocene (<8 Ma) progradation of the fluvial part of the delta (Tipam Group) routed trans‐Himalayan sediment over the shelf edge to the Nicobar Fan. We propose that Miocene progradation of the ancestral Brahmaputra delta reflects increasing rates of erosion and sea level fall during intensification of the South Asian Monsoon after the Miocene Climate Optimum, contemporaneous with a pulse of tectonic uplift of the Himalayan hinterland and Tibet.
Deep Residual Convolutional Neural Network Combining Dropout and Transfer Learning for ENSO Forecasting
Authors: Hu Jie , Weng Bin , Huang Tianqiang , Gao Jianyun , Ye Feng , You Lijun
Published: November 2021

To improve EI Niño‐Southern Oscillation (ENSO) amplitude and type forecast, we propose a model based on a deep residual convolutional neural network with few parameters. We leverage dropout and transfer learning to overcome the challenge of insufficient data in model training process. By applying the dropout technique, the model effectively predicts the Niño3.4 Index at a lead time of 20 months during the 1984–2017 evaluation period, which is three more months than that by the existing optimal model. Moreover, with homogeneous transfer learning this model precisely predicts the Oceanic Niño Index up to 18 months in advance. Using heterogeneous transfer learning this model achieved 83.3% accuracy for forecasting the 12‐month‐lead EI Niño type. These results suggest that our proposed model can enhance the ENSO prediction performance.
Mapping the Sensitivity of the Amundsen Sea Embayment to Changes in External Forcings Using Automatic Differentiation
Authors: Morlighem Mathieu , Goldberg Daniel , Dias dos Santos Thiago , Lee Jane , Sagebaum Max
Published: November 2021

Thwaites and Pine Island Glaciers as well as other ice streams in West Antarctica have been changing dramatically over the past decades. Although changes in ocean conditions are likely the primary driver of these changes, it remains unclear where other processes could cause more mass loss. By employing Automatic Differentiation and two independent ice‐sheet models, we construct maps of the sensitivity of the volume above floatation to changes in ocean‐induced melt rates, ice rigidity, basal friction, and surface mass balance. We find that changes in basal melt close to the grounding lines and along shear margins have a larger impact on the glaciers' final volume. The glaciers are sensitive to changes in basal friction on regions close to the grounding lines, while changes in ice rigidity has a larger impact along the shear margins of Pine Island. The sensitivity to surface mass balance is uniform over grounded ice.
Tropical Pacific Forcing of Hydroclimate in the Source Area of the Yellow River
Authors: Liu Guangxin , He Shaoneng , Wong Minn Lin , Zou Yafei , He Haibo , E Chongyi , Chawchai Sakonvan , Zheng Hongbo , Li Xiangzhong
Published: November 2021

The source area of the Yellow River (SAYR) contributes over one third of the basin discharge and bears disproportionate significance to water conservation in China. Hydroclimate changes in the SAYR, therefore, have potential far‐reaching socioeconomic consequences. However, the major drivers of the SAYR hydroclimate remain poorly understood, largely due to limited hydroclimatic records. Here, we analyzed the organic, carbonate contents and stable isotopes of 14C‐dated sediments from Ngoring Lake to reconstruct regional hydroclimate spanning the last ∼2,000 years. The results suggest that the SAYR experienced a near‐millennium‐long drying trend since the Medieval Warm Period, regardless of temperature changes and meltwater inputs. This trend, coherent with hydroclimate records from north China, is likely forced by a reduction in tropical Pacific zonal sea surface temperature gradient. Furthermore, our records have significant implications for other parts of the Tibetan Plateau that will likely develop similar hydroclimate conditions to the SAYR in the future.
The Role of Diffuse Electron Precipitation in the Formation of Subauroral Polarization Streams
Authors: Lin Dong , Sorathia Kareem , Wang Wenbin , Merkin Viacheslav , Bao Shanshan , Pham Kevin , Wiltberger Michael , Shi Xueling , Toffoletto Frank , Michael Adam , Lyon John , Garretson Jeffrey , Anderson Brian
Published: November 2021

The role of diffuse electron precipitation in the formation of subauroral polarization streams (SAPS) is investigated with the Multiscale Atmosphere‐Geospace Environment (MAGE) model. Diffuse precipitation is derived from the distribution of drifting electrons. SAPS manifest themselves as a separate mesoscale flow channel in the duskside ionosphere, which gradually merges with the primary auroral convection toward dayside as the equatorward auroral boundary approaches the poleward Region‐2 field‐aligned currents (FACs) boundary. SAPS expand to lower latitudes and toward the nightside during the main phase of a geomagnetic storm, associated with magnetotail earthward plasma flows building up the ring current and intensifying Region‐2 FACs and electron precipitation. SAPS shrink poleward and sunward as the interplanetary magnetic field turns northward. When diffuse precipitation is turned off in a controlled MAGE simulation, ring current and duskside Region‐2 FACs become weaker, but subauroral zonal ion drifts are still comparable to auroral convection. However, subauroral and auroral convection manifest as a single broad flow channel without showing any mesoscale structure. SAPS overlap with the downward Region‐2 FACs equatorward of diffuse precipitation, where poleward electric fields are strong due to a low conductance in the subauroral ionosphere. The Region‐2 FACs extend to latitudes lower than the diffuse precipitation because the ring current protons penetrate closer to the Earth than the electrons do. This study reproduces the key physics of SAPS formation and their evolution in the coupled magnetosphere‐ionosphere during a geomagnetic storm. Diffuse electron precipitation is demonstrated to play a critical role in determining SAPS location and structure.
Lithosphere Structure and Seismic Anisotropy Offshore Eastern North America: Implications for Continental Breakup and Ultra‐Slow Spreading Dynamics
Authors: Russell J. B. , Gaherty J. B.
Published: November 2021

The breakup of supercontinent Pangea occurred ∼200 Ma forming the Eastern North American Margin (ENAM). Yet, the precise timing and mechanics of breakup and onset of seafloor spreading remain poorly constrained. We investigate the relict lithosphere offshore eastern North America using ambient‐noise Rayleigh‐wave phase velocity (12–32 s) and azimuthal anisotropy (17–32 s) at the ENAM Community Seismic Experiment (CSE). Incorporating previous constraints on crustal structure, we construct a shear velocity model for the crust and upper ∼60 km of the mantle beneath the ENAM‐CSE. A low‐velocity lid (VS of 4.4–4.55 km/s) is revealed in the upper 15–20 km of the mantle that extends ∼200 km from the margin, terminating at the Blake Spur Magnetic Anomaly (BSMA). East of the BSMA, velocities are fast (>4.6 km/s) and characteristic of typical oceanic mantle lithosphere. We interpret the low‐velocity lid as stretched continental mantle lithosphere embedded with up to ∼15% retained gabbro. This implies that the BSMA marks successful breakup and onset of seafloor spreading ∼170 Ma, consistent with ENAM‐CSE active‐source studies that argue for breakup ∼25 Myr later than previously thought. We observe margin‐parallel Rayleigh‐wave azimuthal anisotropy (2%–4% peak‐to‐peak) in the lithosphere that approximately correlates with absolute plate motion (APM) at the time of spreading. We hypothesize that lithosphere formed during ultra‐slow seafloor spreading records APM‐modified olivine fabric rather than spreading‐parallel fabric typical of higher spreading rates. This work highlights the importance of present‐day passive margins for improving understanding of the fundamental rift‐to‐drift transition.
Formation of an Intrathermocline Eddy Triggered by the Coastal‐Trapped Wave in the Northern Bay of Bengal
Authors: Jithin A. K. , Francis P. A.
Published: November 2021

The present study investigates the characteristics and mechanism of intrathermocline eddy (ITE) formation in the northern Bay of Bengal (BoB) using observations from Research Moored Array for African–Asian–Australian Monsoon Analysis and Prediction (RAMA) buoys moored at 15°N, 12°N, and 8°N along 90°E and simulations from a high‐resolution numerical model. Among the RAMA locations, a relatively large number of anticyclonic ITEs are observed in the northern parts (15°N) compared to the other two (12°N and 8°N). The observed ITEs are characterized by a double‐convex shape of isotherms in the thermocline with a vertical extent of about 100–200 m and a positive sea level anomaly in the surface. Water mass properties show that Andaman Sea (AS) water is trapped inside the core of the ITEs. Trajectories of these ITEs (especially at 15°N) suggest that most of them originated in the vicinity of Preparis Channel, the northernmost passage between BoB and AS. Our study shows that vorticity developed downstream of Preparis Channel due to the strong subsurface flow (∼100 cm/s), which carries AS water into the BoB, results in the formation of observed anticyclonic ITE in the northern BoB. Further analysis revealed that this strong subsurface flow through the Preparis Channel is caused by the propagation of downwelling coastal‐trapped waves along the boundaries of BoB, which originates from the equatorial Indian Ocean. Our study suggests that ITEs could be an important pathway of water mass distribution in the intermediate layers in this region.
Vertical Variations of Cloud Microphysical Relationships in Marine Stratocumulus Clouds Observed During the ACE‐ENA Campaign
Authors: Yeom Jae Min , Yum Seong Soo , Shaw Raymond A. , La Inyeob , Wang Jian , Lu Chunsong , Liu Yangang , Mei Fan , Schmid Beat , Matthews Alyssa
Published: November 2021

This study examines the vertical variations of cloud microphysical relationships and their implications to cloud microphysical processes in marine stratocumulus clouds using in‐situ aircraft observations during the Aerosol and Cloud Experiments in Eastern North Atlantic (ACE‐ENA) field campaign. A new diagram with a coordinate system based on cloud droplet liquid water content (Lc) and phase relaxation time scale is proposed to investigate mixing mechanisms. This new diagram analysis shows that the inhomogeneous mixing trait is dominant near the cloud top, but homogeneous mixing trait is stronger at lower altitudes. The relevant scale parameters (i.e., transition length scale and transition scale number) also indicate a high likelihood of inhomogeneous mixing. The relationship between Lc and standard deviation of droplet radius (σR) clearly shows the vertical transition: the correlation between Lc and σR is positive at lower cloud altitudes, but it becomes negative as altitude increases. Such a vertical transition is consistent with the vertical circulation mixing, modulating the cloud microphysical relationships to suggest homogeneous mixing at a significant depth from the cloud top.
Contribution of the Southern Annular Mode to Variations in Water Isotopes of Daily Precipitation at Dome Fuji, East Antarctica
Authors: Kino Kanon , Okazaki Atsushi , Cauquoin Alexandre , Yoshimura Kei
Published: November 2021

Water isotopes measured in Antarctic ice cores enable reconstruction at the first order of the past temperature variations. However, the seasonality of the precipitation and episodic events, including synoptic‐scale disturbances, influence the isotopic signals recorded in ice cores. In this study, we adopted an isotope‐enabled atmospheric general circulation model from 1981 to 2010 to investigate variations in climatic factors in δ18O of precipitation (δ18Op) at Dome Fuji, East Antarctica. The Southern Annular Mode (SAM), the primary mode of atmospheric circulation in the southern midhigh latitudes, significantly contributes to the isotope signals. Positive δ18Op anomalies, especially in the austral winter, are linked to the negative polarity of the SAM, which weakens westerly winds and increases the southward inflow of water vapor flux. Daily variations in temperature and δ18Op in Dome Fuji are significantly small in the austral summer, and their contribution to the annual signals is limited. The isotope signals driven by the SAM are a locational feature of Dome Fuji, related to the asymmetric component of the large‐scale atmospheric pattern.
Uncertainty of SW Cloud Radiative Effect in Atmospheric Models Due to the Parameterization of Liquid Cloud Optical Properties
Authors: Jahangir E. , Libois Q. , Couvreux F. , Vié B. , Saint‐Martin D.
Published: November 2021

Clouds are largely responsible for the spread of climate models predictions. Here we focus on the uncertainties in cloud shortwave radiative effect due to the parameterization of liquid cloud single scattering properties (SSPs) from liquid water content (LWC) and droplet number concentration (N), named parameterization of cloud optical properties. Uncertainties arise from not accounting for the droplet size distribution (DSD)—which affects the estimation of the effective radius (reff) and modulates the reff‐dependency of the SSPs—and from averaging SSPs over wide spectral bands. To assess these uncertainties a series of reff‐dependent SSPs parameterizations corresponding to various DSDs and spectral averaging methods are derived and implemented in a radiative code. Combined with the DSD‐dependent estimation of reff they are used to compute the bulk radiative properties (reflectance, transmittance, absorptance) of various clouds (defined in terms of LWC and N), including a homogeneous cloud, more realistic case studies, and outputs of a climate model. The results show that the cloud radiative forcing can vary up to 20% depending on the assumed DSD. Likewise, differences up to 20% are obtained for heating rates. The estimation of reff is the main source of uncertainty, while the SSPs parameterization contributes to around 20% of the total uncertainty. Spectral averaging is less an issue, except for atmospheric absorption. Overall, global shortwave cloud radiative effect can vary by 6 W m−2 depending on the assumed DSD shape, which is about 13% of the best observational estimate.
Identifying Stagnation Zones and Reverse Flow Caused by River‐Aquifer Interaction: An Approach Based on Polynomial Chaos Expansions
Authors: Merchán‐Rivera P. , Wohlmuth B. , Chiogna G.
Published: November 2021

Fluctuating stream stages and peak‐flow events can significantly influence the interactions between streams and aquifers and modify the hydraulic gradient, the flux exchange and the subsurface flow paths. As a result, stagnation zones and reverse flow may appear in different parts of an aquifer and at different times. These features of the flow field play a relevant role in the transport, transformation, and residence time of solutes, pollutants, and nutrients in the subsurface. However, their identification using numerical models is complex not only because of highly nonlinear dynamics, but also due to significant uncertainties in the model input data which propagate into the quantities of interest. In this work, we use an approach based on polynomial chaos expansions to map the probability of occurrence of stagnation zones and reverse flow during a flood event. We quantify the propagation of uncertainty into the groundwater flow field due to the applied river boundary conditions. Then, we evaluate the responses of the posterior probabilities in an element‐wise fashion using a set of flow classification criteria and kernel density estimations. The proposed methodology is flexible because it employs a nonintrusive pseudo‐spectral technique and, consequently, it can be applied straightforwardly in preexisting models. The regions near the confluence of two streams in the studied area are prone to present transient stagnation and reverse flow.
Signaling pathways and intervention therapies in sepsis
Authors: Zhang Yun-yu , Ning Bo-tao
Published: November 2021

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced understanding of host–microorganism interaction has gradually unmasked the genuine nature of sepsis, guiding toward new definition and novel therapeutic approaches. Diverse clinical manifestations and outcomes among infectious patients have suggested the heterogeneity of immunopathology, while systemic inflammatory responses and deteriorating organ function observed in critically ill patients imply the extensively hyperactivated cascades by the host defense system. From focusing on microorganism pathogenicity, research interests have turned toward the molecular basis of host responses. Though progress has been made regarding recognition and management of clinical sepsis, incidence and mortality rate remain high. Furthermore, clinical trials of therapeutics have failed to obtain promising results. As far as we know, there was no systematic review addressing sepsis-related molecular signaling pathways and intervention therapy in literature. Increasing studies have succeeded to confirm novel functions of involved signaling pathways and comment on efficacy of intervention therapies amid sepsis. However, few of these studies attempt to elucidate the underlining mechanism in progression of sepsis, while other failed to integrate preliminary findings and describe in a broader view. This review focuses on the important signaling pathways, potential molecular mechanism, and pathway-associated therapy in sepsis. Host-derived molecules interacting with activated cells possess pivotal role for sepsis pathogenesis by dynamic regulation of signaling pathways. Cross-talk and functions of these molecules are also discussed in detail. Lastly, potential novel therapeutic strategies precisely targeting on signaling pathways and molecules are mentioned.
Translation stalling proline motifs are enriched in slow-growing, thermophilic, and multicellular bacteria
Authors: Brewer Tess E , Wagner Andreas
Published: November 2021

Rapid bacterial growth depends on the speed at which ribosomes can translate mRNA into proteins. mRNAs that encode successive stretches of proline can cause ribosomes to stall, substantially reducing translation speed. Such stalling is especially detrimental for species that must grow and divide rapidly. Here, we focus on di-prolyl motifs (XXPPX) and ask whether their prevalence varies with growth rate. To find out we conducted a broad survey of such motifs in >3000 bacterial genomes across 35 phyla. Indeed, fast-growing species encode fewer motifs than slow-growing species, especially in highly expressed proteins. We also found many di-prolyl motifs within thermophiles, where prolines can help maintain proteome stability. Moreover, bacteria with complex, multicellular lifecycles also encode many di-prolyl motifs. This is especially evident in the slow-growing phylum Myxococcota. Bacteria in this phylum encode many serine-threonine kinases, and many di-prolyl motifs at potential phosphorylation sites within these kinases. Serine-threonine kinases are involved in cell signaling and help regulate developmental processes linked to multicellularity in the Myxococcota. Altogether, our observations suggest that weakened selection on translational rate, whether due to slow or thermophilic growth, may allow di-prolyl motifs to take on new roles in biological processes that are unrelated to translational rate.
Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank
Authors: Winterton Adriano , Bettella Francesco , de Lange Ann-Marie G. , Haram Marit , Steen Nils Eiel , Westlye Lars T. , Andreassen Ole A. , Quintana Daniel S.
Published: November 2021

Oxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin’s role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses.
Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture
Authors: Álvarez Eva G. , Demeulemeester Jonas , Otero Paula , Jolly Clemency , García-Souto Daniel , Pequeño-Valtierra Ana , Zamora Jorge , Tojo Marta , Temes Javier , Baez-Ortega Adrian , Rodriguez-Martin Bernardo , Oitaben Ana , Bruzos Alicia L. , Martínez-Fernández Mónica , Haase Kerstin , Zumalave Sonia , Abal Rosanna , Rodríguez-Castro Jorge , Rodriguez-Casanova Aitor , Diaz-Lagares Angel , Li Yilong , Raine Keiran M. , Butler Adam P. , Otero Iago , Ono Atsushi , Aikata Hiroshi , Chayama Kazuaki , Ueno Masaki , Hayami Shinya , Yamaue Hiroki , Maejima Kazuhiro , Blanco Miguel G. , Forns Xavier , Rivas Carmen , Ruiz-Bañobre Juan , Pérez-del-Pulgar Sofía , Torres-Ruiz Raúl , Rodriguez-Perales Sandra , Garaigorta Urtzi , Campbell Peter J. , Nakagawa Hidewaki , Van Loo Peter , Tubio Jose M. C.
Published: November 2021

Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration.
Hydrothermal plumes as hotspots for deep-ocean heterotrophic microbial biomass production
Authors: Cathalot Cécile , Roussel Erwan G. , Perhirin Antoine , Creff Vanessa , Donval Jean-Pierre , Guyader Vivien , Roullet Guillaume , Gula Jonathan , Tamburini Christian , Garel Marc , Godfroy Anne , Sarradin Pierre-Marie
Published: November 2021

Carbon budgets of hydrothermal plumes result from the balance between carbon sinks through plume chemoautotrophic processes and carbon release via microbial respiration. However, the lack of comprehensive analysis of the metabolic processes and biomass production rates hinders an accurate estimate of their contribution to the deep ocean carbon cycle. Here, we use a biogeochemical model to estimate the autotrophic and heterotrophic production rates of microbial communities in hydrothermal plumes and validate it with in situ data. We show how substrate limitation might prevent net chemolithoautotrophic production in hydrothermal plumes. Elevated prokaryotic heterotrophic production rates (up to 0.9 gCm−2y−1) compared to the surrounding seawater could lead to 0.05 GtCy−1 of C-biomass produced through chemoorganotrophy within hydrothermal plumes, similar to the Particulate Organic Carbon (POC) export fluxes reported in the deep ocean. We conclude that hydrothermal plumes must be accounted for as significant deep sources of POC in ocean carbon budgets.
Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
Authors: Zhang Qianqian , Cheng Sijin , Wang Yongzhi , Wang Mengdi , Lu Yufeng , Wen Zengqi , Ge Yuxin , Ma Qiang , Chen Youqiao , Zhang Yaowu , Cao Ren , Li Min , Liu Weihao , Wang Bo , Wu Qian , Jia Wenqing , Wang Xiaoqun
Published: November 2021

Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.
Photoluminescence mechanism of carbon dots: triggering high-color-purity red fluorescence emission through edge amino protonation
Authors: Zhang Qing , Wang Ruoyu , Feng Bowen , Zhong Xiaoxia , Ostrikov Kostya
Published: November 2021

Due to complex structure and surface functionalities, photoluminescence mechanisms of Carbon Dots are unknown, and it is challenging to synthesize Carbon Dots to achieve the desired optical properties. Herein, Carbon Dots simultaneously exhibiting high-color-purity (FWHM~24 nm) long wavelength one-photon fluorescence emission at 620 nm and NIR induced two-photon fluorescence emission at 630 and 680 nm are prepared by edge amino protonation treatment. Systematic analysis reveals that the protonation of 2,3-diaminophenazine changes the molecular state of Carbon Dots, decreases the photon transition band gap, and triggers red fluorescence emission with the dramatically narrowed peak width. As the oxidation products of reactant o-phenylendiamine, the emergence of 2,3-diaminophenazine as a photoluminescence determiner suggests that fluorophore products of precursor conversion are viable determinants of the desired luminescence properties of Carbon Dots. This work shows a new way for predicting and controlling photoluminescence properties of Carbon Dots, and may guide the development of tunable Carbon Dots for a broad range of applications.
Thermal dynamics and electronic temperature waves in layered correlated materials
Authors: Mazza Giacomo , Gandolfi Marco , Capone Massimo , Banfi Francesco , Giannetti Claudio
Published: November 2021

Understanding the mechanism of heat transfer in nanoscale devices remains one of the greatest intellectual challenges in the field of thermal dynamics, by far the most relevant under an applicative standpoint. When thermal dynamics is confined to the nanoscale, the characteristic timescales become ultrafast, engendering the failure of the common description of energy propagation and paving the way to unconventional phenomena such as wave-like temperature propagation. Here, we explore layered strongly correlated materials as a platform to identify and control unconventional electronic heat transfer phenomena. We demonstrate that these systems can be tailored to sustain a wide spectrum of electronic heat transport regimes, ranging from ballistic, to hydrodynamic all the way to diffusive. Within the hydrodynamic regime, wave-like temperature oscillations are predicted up to room temperature. The interaction strength can be exploited as a knob to control the dynamics of temperature waves as well as the onset of different thermal transport regimes.
A full gap above the Fermi level: the charge density wave of monolayer VS2
Authors: van Efferen Camiel , Berges Jan , Hall Joshua , van Loon Erik , Kraus Stefan , Schobert Arne , Wekking Tobias , Huttmann Felix , Plaar Eline , Rothenbach Nico , Ollefs Katharina , Arruda Lucas Machado , Brookes Nick , Schönhoff Gunnar , Kummer Kurt , Wende Heiko , Wehling Tim , Michely Thomas
Published: November 2021

In the standard model of charge density wave (CDW) transitions, the displacement along a single phonon mode lowers the total electronic energy by creating a gap at the Fermi level, making the CDW a metal–insulator transition. Here, using scanning tunneling microscopy and spectroscopy and ab initio calculations, we show that VS2 realizes a CDW which stands out of this standard model. There is a full CDW gap residing in the unoccupied states of monolayer VS2. At the Fermi level, the CDW induces a topological metal-metal (Lifshitz) transition. Non-linear coupling of transverse and longitudinal phonons is essential for the formation of the CDW and the full gap above the Fermi level. Additionally, x-ray magnetic circular dichroism reveals the absence of net magnetization in this phase, pointing to coexisting charge and spin density waves in the ground state.
Ultra-rapid and highly efficient enrichment of organic pollutants via magnetic mesoporous nanosponge for ultrasensitive nanosensors
Authors: Zhang Lingling , Guo Yu , Hao Rui , Shi Yafei , You Hongjun , Nan Hu , Dai Yanzhu , Liu Danjun , Lei Dangyuan , Fang Jixiang
Published: November 2021

Currently, owing to the single-molecule-level sensitivity and highly informative spectroscopic characteristics, surface-enhanced Raman scattering (SERS) is regarded as the most direct and effective detection technique. However, SERS still faces several challenges in its practical applications, such as the complex matrix interferences, and low sensitivity to the molecules of intrinsic small cross-sections or weak affinity to the surface of metals. Here, we show an enrichment-typed sensing strategy with both excellent selectivity and ultrahigh detection sensitivity based on a powerful porous composite material, called mesoporous nanosponge. The nanosponge consists of porous β-cyclodextrin polymers immobilized with magnetic NPs, demonstrating remarkable capability of effective and fast removal of organic micropollutants, e.g., ~90% removal efficiency within ~1 min, and an enrichment factor up to ~103. By means of this current enrichment strategy, the limit of detection for typical organic pollutants can be significantly improved by 2~3 orders of magnitude. Consequently, the current enrichment strategy is proved to be applicable in a variety of fields for portable and fast detection, such as Raman and fluorescent sensing.
High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer
Authors: Rogic Anita , Pant Ila , Grumolato Luca , Fernandez-Rodriguez Ruben , Edwards Andrew , Das Suvendu , Sun Aaron , Yao Shen , Qiao Rui , Jaffer Shabnam , Sachidanandam Ravi , Akturk Guray , Karlic Rosa , Skobe Mihaela , Aaronson Stuart A.
Published: November 2021

Inflammatory Breast Cancer (IBC) is a highly aggressive malignancy with distinct clinical and histopathological features whose molecular basis is unresolved. Here we describe a human IBC cell line, A3250, that recapitulates key IBC features in a mouse xenograft model, including skin erythema, diffuse tumor growth, dermal lymphatic invasion, and extensive metastases. A3250 cells express very high levels of the CCL2 chemokine and induce tumors enriched in macrophages. CCL2 knockdown leads to a striking reduction in macrophage densities, tumor proliferation, skin erythema, and metastasis. These results establish IBC-derived CCL2 as a key factor driving macrophage expansion, and indirectly tumor growth, with transcriptomic analysis demonstrating the activation of multiple inflammatory pathways. Finally, primary human IBCs exhibit macrophage infiltration and an enriched macrophage RNA signature. Thus, this human IBC model provides insight into the distinctive biology of IBC, and highlights potential therapeutic approaches to this deadly disease.
Interaction of two MADS-box genes leads to growth phenotype divergence of all-flesh type of tomatoes
Authors: Huang Baowen , Hu Guojian , Wang Keke , Frasse Pierre , Maza Elie , Djari Anis , Deng Wei , Pirrello Julien , Burlat Vincent , Pons Clara , Granell Antonio , Li Zhengguo , van der Rest Benoît , Bouzayen Mondher
Published: November 2021

All-flesh tomato cultivars are devoid of locular gel and exhibit enhanced firmness and improved postharvest storage. Here, we show that SlMBP3 is a master regulator of locular tissue in tomato fruit and that a deletion at the gene locus underpins the All-flesh trait. Intriguingly, All-flesh varieties lack the deleterious phenotypes reported previously for SlMBP3 under-expressing lines and which preclude any potential commercial use. We resolve the causal factor for this phenotypic divergence through the discovery of a natural mutation at the SlAGL11 locus, a close homolog of SlMBP3. Misexpressing SlMBP3 impairs locular gel formation through massive transcriptomic reprogramming at initial phases of fruit development. SlMBP3 influences locule gel formation by controlling cell cycle and cell expansion genes, indicating that important components of fruit softening are determined at early pre-ripening stages. Our findings define potential breeding targets for improved texture in tomato and possibly other fleshy fruits.
N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization
Authors: Freibert Sven-A. , Boniecki Michal T. , Stümpfig Claudia , Schulz Vinzent , Krapoth Nils , Winge Dennis R. , Mühlenhoff Ulrich , Stehling Oliver , Cygler Miroslaw , Lill Roland
Published: November 2021

Synthesis of iron-sulfur (Fe/S) clusters in living cells requires scaffold proteins for both facile synthesis and subsequent transfer of clusters to target apoproteins. The human mitochondrial ISCU2 scaffold protein is part of the core ISC (iron-sulfur cluster assembly) complex that synthesizes a bridging [2Fe-2S] cluster on dimeric ISCU2. Initial iron and sulfur loading onto monomeric ISCU2 have been elucidated biochemically, yet subsequent [2Fe-2S] cluster formation and dimerization of ISCU2 is mechanistically ill-defined. Our structural, biochemical and cell biological experiments now identify a crucial function of the universally conserved N-terminal Tyr35 of ISCU2 for these late reactions. Mixing two, per se non-functional ISCU2 mutant proteins with oppositely charged Asp35 and Lys35 residues, both bound to different cysteine desulfurase complexes NFS1-ISD11-ACP, restores wild-type ISCU2 maturation demonstrating that ionic forces can replace native Tyr-Tyr interactions during dimerization-induced [2Fe-2S] cluster formation. Our studies define the essential mechanistic role of Tyr35 in the reaction cycle of de novo mitochondrial [2Fe-2S] cluster synthesis.
A benchmark study of simulation methods for single-cell RNA sequencing data
Authors: Cao Yue , Yang Pengyi , Yang Jean Yee Hwa
Published: November 2021

Single-cell RNA-seq (scRNA-seq) data simulation is critical for evaluating computational methods for analysing scRNA-seq data especially when ground truth is experimentally unattainable. The reliability of evaluation depends on the ability of simulation methods to capture properties of experimental data. However, while many scRNA-seq data simulation methods have been proposed, a systematic evaluation of these methods is lacking. We develop a comprehensive evaluation framework, SimBench, including a kernel density estimation measure to benchmark 12 simulation methods through 35 scRNA-seq experimental datasets. We evaluate the simulation methods on a panel of data properties, ability to maintain biological signals, scalability and applicability. Our benchmark uncovers performance differences among the methods and highlights the varying difficulties in simulating data characteristics. Furthermore, we identify several limitations including maintaining heterogeneity of distribution. These results, together with the framework and datasets made publicly available as R packages, will guide simulation methods selection and their future development.
A transposon expression burst accompanies the activation of Y-chromosome fertility genes during Drosophila spermatogenesis
Authors: Lawlor Matthew A. , Cao Weihuan , Ellison Christopher E.
Published: November 2021

Transposable elements (TEs) must replicate in germline cells to pass novel insertions to offspring. In Drosophila melanogaster ovaries, TEs can exploit specific developmental windows of opportunity to evade host silencing and increase their copy numbers. However, TE activity and host silencing in the distinct cell types of Drosophila testis are not well understood. Here, we reanalyze publicly available single-cell RNA-seq datasets to quantify TE expression in the distinct cell types of the Drosophila testis. We develop a method for identification of TE and host gene expression modules and find that a distinct population of early spermatocytes expresses a large number of TEs at much higher levels than other germline and somatic components of the testes. This burst of TE expression coincides with the activation of Y chromosome fertility factors and spermatocyte-specific transcriptional regulators, as well as downregulation of many components of the piRNA pathway. The TEs expressed by this cell population are specifically enriched on the Y chromosome and depleted on the X chromosome, relative to other active TEs. These data suggest that some TEs may achieve high insertional activity in males by exploiting a window of opportunity for mobilization created by the activation of spermatocyte-specific and Y chromosome-specific transcriptional programs.
Network medicine for disease module identification and drug repurposing with the NeDRex platform
Authors: Sadegh Sepideh , Skelton James , Anastasi Elisa , Bernett Judith , Blumenthal David B. , Galindez Gihanna , Salgado-Albarrán Marisol , Lazareva Olga , Flanagan Keith , Cockell Simon , Nogales Cristian , Casas Ana I. , Schmidt Harald H. H. W. , Baumbach Jan , Wipat Anil , Kacprowski Tim
Published: November 2021

Traditional drug discovery faces a severe efficacy crisis. Repurposing of registered drugs provides an alternative with lower costs and faster drug development timelines. However, the data necessary for the identification of disease modules, i.e. pathways and sub-networks describing the mechanisms of complex diseases which contain potential drug targets, are scattered across independent databases. Moreover, existing studies are limited to predictions for specific diseases or non-translational algorithmic approaches. There is an unmet need for adaptable tools allowing biomedical researchers to employ network-based drug repurposing approaches for their individual use cases. We close this gap with NeDRex, an integrative and interactive platform for network-based drug repurposing and disease module discovery. NeDRex integrates ten different data sources covering genes, drugs, drug targets, disease annotations, and their relationships. NeDRex allows for constructing heterogeneous biological networks, mining them for disease modules, prioritizing drugs targeting disease mechanisms, and statistical validation. We demonstrate the utility of NeDRex in five specific use-cases.
Gene editing enables rapid engineering of complex antibiotic assembly lines
Authors: Thong Wei Li , Zhang Yingxin , Zhuo Ying , Robins Katherine J. , Fyans Joanna K. , Herbert Abigail J. , Law Brian J. C. , Micklefield Jason
Published: November 2021

Re-engineering biosynthetic assembly lines, including nonribosomal peptide synthetases (NRPS) and related megasynthase enzymes, is a powerful route to new antibiotics and other bioactive natural products that are too complex for chemical synthesis. However, engineering megasynthases is very challenging using current methods. Here, we describe how CRISPR-Cas9 gene editing can be exploited to rapidly engineer one of the most complex megasynthase assembly lines in nature, the 2.0 MDa NRPS enzymes that deliver the lipopeptide antibiotic enduracidin. Gene editing was used to exchange subdomains within the NRPS, altering substrate selectivity, leading to ten new lipopeptide variants in good yields. In contrast, attempts to engineer the same NRPS using a conventional homologous recombination-mediated gene knockout and complementation approach resulted in only traces of new enduracidin variants. In addition to exchanging subdomains within the enduracidin NRPS, subdomains from a range of NRPS enzymes of diverse bacterial origins were also successfully utilized.
Structural and functional analysis of the promiscuous AcrB and AdeB efflux pumps suggests different drug binding mechanisms
Authors: Ornik-Cha Alina , Wilhelm Julia , Kobylka Jessica , Sjuts Hanno , Vargiu Attilio V. , Malloci Giuliano , Reitz Julian , Seybert Anja , Frangakis Achilleas S. , Pos Klaas M.
Published: November 2021

Upon antibiotic stress Gram-negative pathogens deploy resistance-nodulation-cell division-type tripartite efflux pumps. These include a H+/drug antiporter module that recognizes structurally diverse substances, including antibiotics. Here, we show the 3.5 Å structure of subunit AdeB from theAcinetobacter baumanniiAdeABC efflux pump solved by single-particle cryo-electron microscopy. The AdeB trimer adopts mainly a resting state with all protomers in a conformation devoid of transport channels or antibiotic binding sites. However, 10% of the protomers adopt a state where three transport channels lead to the closed substrate (deep) binding pocket. A comparison between drug binding of AdeB andEscherichia coliAcrB is made via activity analysis of 20 AdeB variants, selected on basis of side chain interactions with antibiotics observed in the AcrB periplasmic domain X-ray co-structures with fusidic acid (2.3 Å), doxycycline (2.1 Å) and levofloxacin (2.7 Å). AdeABC, compared to AcrAB-TolC, confers higher resistance toE. colitowards polyaromatic compounds and lower resistance towards antibiotic compounds.