bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forward Modeling of the Phobos Tides and Applications to the First Martian Year of the InSight Mission
Authors: Pou L. , Nimmo F. , Lognonné P. , Mimoun D. , Garcia R. F. , Pinot B. , Rivoldini A. , Banfield D. , Banerdt W. B. 
Published: June 2021

AbstractThe tidal response of Mars, due to the Sun and the Martian moons, Phobos and Deimos, provides information about the interior structure of Mars. By using the Very Broad Band (VBB) seismometer of Seismic Experiment for Interior Structure (SEIS) as a gravimeter on the surface of Mars, the InSight mission will provide the long‐period data suited to tidal analysis: most notably, the proximity of Phobos implies that degree 2, 3, 4, and further tides will be detectable by the VBB and are expected to provide information about the rheology at different depths within Mars. In order to expedite the recovery of these tidal signals in the SEIS measurements, we model the tides raised by Phobos using a tidal potential deduced from JPL Horizons ephemerides. From this potential, we calculate the expected tidal acceleration at InSight's location and gravimetric factors using a set of plausible interior models of Mars. To simulate the expected long period signal on the VBB seismometer, we use the InSight Auxiliary Payload Sensor Suite data to model the noise seen at low frequency by SEIS mainly due to temperature and pressure variations. Based on this synthetic signal, by applying filtering methods such as stacking and matched filtering to these synthetic data, we show that by recovering the gravimetric factors, it should be possible to constrain the state of the core and its size with an accuracy of 125 km after two Earth years.
A ∼12 Myr Miocene Record of East Asian Monsoon Variability From the South China Sea
Authors: Holbourn Ann , Kuhnt Wolfgang , Clemens Steven C. , Heslop David 
Published: June 2021

AbstractThe long‐term evolution of the East Asian Monsoon and the processes controlling its variability under changing climate boundary conditions remain enigmatic. Here, we integrate new and published high‐resolution planktic and benthic foraminiferal isotope data with proxy records for chemical weathering derived from diffuse reflectance spectroscopy at Ocean Drilling Program Site 1146 (South China Sea) to reconstruct the evolution of the summer monsoon between ∼17 and 5 Ma. Our records show that an overall warm and humid tropical climate prevailed over southeastern Asia during the Miocene Climatic Optimum, suggesting northward expansion of the tropical rain belt in response to greenhouse gas forcing. By contrast, monsoon seasonality increased during the middle Miocene Climatic Transition in tandem with Antarctic glacial expansion and global cooling. Substantial weakening of the summer monsoon between ∼12.7 and 10.9 Ma supports that decreased weathering and riverine input of nutrients and alkalinity contributed to carbonate depletion in the deep ocean during the Carbonate Crash. Intensification of monsoonal circulation and strengthening of the biological pump through the late Miocene promoted carbon burial, drawdown of atmospheric CO2, and climate cooling during the Biogenic Bloom. These results underscore the dynamic evolution of the East Asian Monsoon throughout the middle to late Miocene. Variations in local insolation forcing and in Southern Hemisphere ice volume, influencing the latitudinal thermal gradient, evaporation‐moisture budgets, and the strength of the tropical convection, exerted major controls on the development of the monsoon.
External cervical resorption—a review of pathogenesis and potential predisposing factors
Authors: Chen Yiming , Huang Ying , Deng Xuliang 
Published: June 2021

AbstractExternal cervical resorption (ECR) refers to a pathological state in which resorption tissues penetrate into the dentin at the cervical aspect of the root. Despite being latent in its initial phase, ECR could cause severe damage to mineralized dental tissue and even involve the pulp if not given timely diagnosis and treatment. Nevertheless, the etiology of ECR is still poorly understood, which adds to the difficulty in early diagnosis. ECR has received growing attention in recent years due to the increasing number of clinical cases. Several potential predisposing factors have been recognized in cross-sectional studies as well as case reports. In the meantime, studies on histopathology and pathogenesis have shed light on possible mechanisms of ECR. This review aims to summarize the latest findings in the pathogenesis and potential predisposing factors of ECR, so as to provide pragmatic reference for clinical practice.
Somatostatin neurons control an alcohol binge drinking prelimbic microcircuit in mice
Authors: Dao Nigel C. , Brockway Dakota F. , Suresh Nair Malini , Sicher Avery R. , Crowley Nicole A. 
Published: June 2021

AbstractSomatostatin (SST) neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance use disorders, including alcohol use disorder (AUD), is not fully characterized. Here, we found that repeated cycles of alcohol binge drinking via the Drinking-in-the-Dark (DID) model led to hypoactivity of SST neurons in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. Alcohol binge drinking disinhibited pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations and reducing spontaneous inhibitory transmission onto pyramidal neurons. Pyramidal neurons additionally displayed increased intrinsic excitability. Direct inhibition of PL pyramidal neurons via hM4Di was sufficient to reduce alcohol binge drinking. Together these data revealed an SST-mediated microcircuit in the PL that modulates the inhibitory dynamics of pyramidal neurons, a major source of output to subcortical targets to drive reward-seeking behaviors and emotional response.
Correction: Phage gene expression and host responses lead to infection-dependent costs of CRISPR immunity
Authors: Meaden Sean , Capria Loris , Alseth Ellinor , Gandon Sylvain , Biswas Ambarish , Lenzi Luca , van Houte Stineke , Westra Edze R 
Published: June 2021

Abstract
A Correction to this paper has been published: https://doi.org/10.1038/s41396-020-00846-1
Degradation of biological macromolecules supports uncultured microbial populations in Guaymas Basin hydrothermal sediments
Authors: Pérez Castro Sherlynette , Borton Mikayla A , Regan Kathleen , Hrabe de Angelis Isabella , Wrighton Kelly C , Teske Andreas P , Strous Marc , Ruff S Emil 
Published: June 2021

Abstract
Hydrothermal sediments contain large numbers of uncultured heterotrophic microbial lineages. Here, we amended Guaymas Basin sediments with proteins, polysaccharides, nucleic acids or lipids under different redox conditions and cultivated heterotrophic thermophiles with the genomic potential for macromolecule degradation. We reconstructed 20 metagenome-assembled genomes (MAGs) of uncultured lineages affiliating with known archaeal and bacterial phyla, including endospore-forming Bacilli and candidate phylum Marinisomatota. One Marinisomatota MAG had 35 different glycoside hydrolases often in multiple copies, seven extracellular CAZymes, six polysaccharide lyases, and multiple sugar transporters. This population has the potential to degrade a broad spectrum of polysaccharides including chitin, cellulose, pectin, alginate, chondroitin, and carrageenan. We also describe thermophiles affiliating with the genera Thermosyntropha, Thermovirga, and Kosmotoga with the capability to make a living on nucleic acids, lipids, or multiple macromolecule classes, respectively. Several populations seemed to lack extracellular enzyme machinery and thus likely scavenged oligo- or monomers (e.g., MAGs affiliating with Archaeoglobus) or metabolic products like hydrogen (e.g., MAGs affiliating with Thermodesulfobacterium or Desulforudaceae). The growth of methanogens or the production of methane was not observed in any condition, indicating that the tested macromolecules are not degraded into substrates for methanogenesis in hydrothermal sediments. We provide new insights into the niches, and genomes of microorganisms that actively degrade abundant necromass macromolecules under oxic, sulfate-reducing, and fermentative thermophilic conditions. These findings improve our understanding of the carbon flow across trophic levels and indicate how primary produced biomass sustains complex and productive ecosystems.
Reductive dissolution of pyrite by methanogenic archaea
Authors: Payne Devon , Spietz Rachel L , Boyd Eric S 
Published: June 2021

Abstract
The formation and fate of pyrite (FeS2) modulates global iron, sulfur, carbon, and oxygen biogeochemical cycles and has done so since early in Earth’s geological history. A longstanding paradigm is that FeS2 is stable at low temperature and is unavailable to microorganisms in the absence of oxygen and oxidative weathering. Here, we show that methanogens can catalyze the reductive dissolution of FeS2 at low temperature (≤38 °C) and utilize dissolution products to meet cellular iron and sulfur demands associated with the biosynthesis of simple and complex co-factors. Direct access to FeS2 is required to catalyze its reduction and/or to assimilate iron monosulfide that likely forms through coupled reductive dissolution and precipitation, consistent with close associations observed between cells and FeS2. These findings demonstrate that FeS2 is bioavailable to anaerobic methanogens and can be mobilized in low temperature anoxic environments. Given that methanogens evolved at least 3.46 Gya, these data indicate that the microbial contribution to the iron and sulfur cycles in ancient and contemporary anoxic environments may be more complex and robust than previously recognized, with impacts on the sources and sinks of iron and sulfur and other bio-essential and thiophilic elements such as nickel and cobalt.
Necroptosis protects against exacerbation of acute pancreatitis
Authors: Boonchan Michittra , Arimochi Hideki , Otsuka Kunihiro , Kobayashi Tomoko , Uehara Hisanori , Jaroonwitchawan Thiranut , Sasaki Yuki , Tsukumo Shin-ichi , Yasutomo Koji 
Published: June 2021

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.
Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy
Authors: Wang Yu-Chen , Wang Xi , Yu Jiaji , Ma Feiyang , Li Zhe , Zhou Yang , Zeng Samuel , Ma Xiaoya , Li Yan-Ruide , Neal Adam , Huang Jie , To Angela , Clarke Nicole , Memarzadeh Sanaz , Pellegrini Matteo , Yang Lili 
Published: June 2021

AbstractTargeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity. MAOI treatment induces TAM reprogramming and suppresses tumor growth in preclinical mouse syngeneic and human xenograft tumor models. Combining MAOI and anti-PD-1 treatments results in synergistic tumor suppression. Clinical data correlation studies associate high intratumoral MAOA expression with poor patient survival in a broad range of cancers. We further demonstrate that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.
Rapid endogenic rock recycling in magmatic arcs
Authors: Li Jun-Yong , Tang Ming , Lee Cin-Ty A. , Wang Xiao-Lei , Gu Zhi-Dong , Xia Xiao-Ping , Wang Di , Du De-Hong , Li Lin-Sen 
Published: June 2021

AbstractIn subduction zones, materials on Earth’s surface can be transported to the deep crust or mantle, but the exact mechanisms and the nature of the recycled materials are not fully understood. Here, we report a set of migmatites from western Yangtze Block, China. These migmatites have similar bulk compositions as forearc sediments. Zircon age distributions and Hf–O isotopes indicate that the precursors of the sediments were predominantly derived from juvenile arc crust itself. Using phase equilibria modeling, we show that the sediments experienced high temperature-to-pressure ratio metamorphism and were most likely transported to deep arc crust by intracrustal thrust faults. By dating the magmatic zircon cores and overgrowth rims, we find that the entire rock cycle, from arc magmatism, to weathering at the surface, then to burial and remelting in the deep crust, took place within ~10 Myr. Our findings highlight thrust faults as an efficient recycling channel in compressional arcs and endogenic recycling as an important mechanism driving internal redistribution and differentiation of arc crust.
The epigenetic regulator LSH maintains fork protection and genomic stability via MacroH2A deposition and RAD51 filament formation
Authors: Xu Xiaoping , Ni Kai , He Yafeng , Ren Jianke , Sun Chongkui , Liu Yie , Aladjem Mirit I. , Burkett Sandra , Finney Richard , Ding Xia , Sharan Shyam K. , Muegge Kathrin 
Published: June 2021

AbstractThe Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is caused by mutations in LSH/HELLS, a chromatin remodeler promoting incorporation of histone variant macroH2A. Here, we demonstrate that LSH depletion results in degradation of nascent DNA at stalled replication forks and the generation of genomic instability. The protection of stalled forks is mediated by macroH2A, whose knockdown mimics LSH depletion and whose overexpression rescues nascent DNA degradation. LSH or macroH2A deficiency leads to an impairment of RAD51 loading, a factor that prevents MRE11 and EXO1 mediated nascent DNA degradation. The defect in RAD51 loading is linked to a disbalance of BRCA1 and 53BP1 accumulation at stalled forks. This is associated with perturbed histone modifications, including abnormal H4K20 methylation that is critical for BRCA1 enrichment and 53BP1 exclusion. Altogether, our results illuminate the mechanism underlying a human syndrome and reveal a critical role of LSH mediated chromatin remodeling in genomic stability.
Aberrant dynamics of cognitive control and motor circuits predict distinct restricted and repetitive behaviors in children with autism
Authors: Supekar Kaustubh , Ryali Srikanth , Mistry Percy , Menon Vinod 
Published: June 2021

AbstractRestricted and repetitive behaviors (RRBs) are a defining clinical feature of autism spectrum disorders (ASD). RRBs are highly heterogeneous with variable expression of circumscribed interests (CI), insistence of sameness (IS) and repetitive motor actions (RM), which are major impediments to effective functioning in individuals with ASD; yet, the neurobiological basis of CI, IS and RM is unknown. Here we evaluate a unified functional brain circuit model of RRBs and test the hypothesis that CI and IS are associated with aberrant cognitive control circuit dynamics, whereas RM is associated with aberrant motor circuit dynamics. Using task-free fMRI data from 96 children, we first demonstrate that time-varying cross-network interactions in cognitive control circuit are significantly reduced and inflexible in children with ASD, and predict CI and IS symptoms, but not RM symptoms. Furthermore, we show that time-varying cross-network interactions in motor circuit are significantly greater in children with ASD, and predict RM symptoms, but not CI or IS symptoms. We confirmed these results using cross-validation analyses. Moreover, we show that brain-clinical symptom relations are not detected with time-averaged functional connectivity analysis. Our findings provide neurobiological support for the validity of RRB subtypes and identify dissociable brain circuit dynamics as a candidate biomarker for a key clinical feature of ASD.
Machine-learning predicts genomic determinants of meiosis-driven structural variation in a eukaryotic pathogen
Authors: Badet Thomas , Fouché Simone , Hartmann Fanny E. , Zala Marcello , Croll Daniel 
Published: June 2021

AbstractSpecies harbor extensive structural variation underpinning recent adaptive evolution. However, the causality between genomic features and the induction of new rearrangements is poorly established. Here, we analyze a global set of telomere-to-telomere genome assemblies of a fungal pathogen of wheat to establish a nucleotide-level map of structural variation. We show that the recent emergence of pesticide resistance has been disproportionally driven by rearrangements. We use machine learning to train a model on structural variation events based on 30 chromosomal sequence features. We show that base composition and gene density are the major determinants of structural variation. Retrotransposons explain most inversion, indel and duplication events. We apply our model toArabidopsis thalianaand show that our approach extends to more complex genomes. Finally, we analyze complete genomes of haploid offspring in a four-generation pedigree. Meiotic crossover locations are enriched for new rearrangements consistent with crossovers being mutational hotspots. The model trained on species-wide structural variation accurately predicts the position of >74% of newly generated variants along the pedigree. The predictive power highlights causality between specific sequence features and the induction of chromosomal rearrangements. Our work demonstrates that training sequence-derived models can accurately identify regions of intrinsic DNA instability in eukaryotic genomes.
Designing zero-dimensional dimer-type all-inorganic perovskites for ultra-fast switching memory
Authors: Park Youngjun , Kim Seong Hun , Lee Donghwa , Lee Jang-Sik 
Published: June 2021

AbstractResistive switching memory that uses halide perovskites (HP) has been considered as next-generation storage devices due to low operation voltage and high on/off ratio. However, the memory still faces challenges for stable operation with fast switching speed, which hinders the practical application. Thus, it should be considered from the stage of designing the HP for memory applications. Here, we design the perovskite memory using a high-throughput screening based on first-principles calculations. Total 696 compositions in four different crystal structures are investigated and essential parameters including stability, vacancy formation, and migration are considered as the descriptor. We select dimer-Cs3Sb2I9 as an optimal HP for memory; the device that uses dimer-Cs3Sb2I9 has ultra-fast switching speed (~20 ns) compared to the device that uses layer-Cs3Sb2I9 (>100 ns). The use of lead-free perovskite avoids environmental problems caused by lead in perovskite. These results demonstrate the feasibility to design the memory with ultra-fast switching speed.
A chromosome-level Camptotheca acuminata genome assembly provides insights into the evolutionary origin of camptothecin biosynthesis
Authors: Kang Minghui , Fu Rao , Zhang Pingyu , Lou Shangling , Yang Xuchen , Chen Yang , Ma Tao , Zhang Yang , Xi Zhenxiang , Liu Jianquan 
Published: June 2021

AbstractCamptothecin and its derivatives are widely used for treating malignant tumors. Previous studies revealed only a limited number of candidate genes for camptothecin biosynthesis in Camptotheca acuminata, and it is still poorly understood how its biosynthesis of camptothecin has evolved. Here, we report a high-quality, chromosome-level C. acuminata genome assembly. We find that C. acuminata experiences an independent whole-genome duplication and numerous genes derive from it are related to camptothecin biosynthesis. Comparing with Catharanthus roseus, the loganic acid O-methyltransferase (LAMT) in C. acuminata fails to convert loganic acid into loganin. Instead, two secologanic acid synthases (SLASs) convert loganic acid to secologanic acid. The functional divergence of the LAMT gene and positive evolution of two SLAS genes, therefore, both contribute greatly to the camptothecin biosynthesis in C. acuminata. Our results emphasize the importance of high-quality genome assembly in identifying genetic changes in the evolutionary origin of a secondary metabolite.
Viral infiltration of pancreatic islets in patients with COVID-19
Authors: Steenblock Charlotte , Richter Stefanie , Berger Ilona , Barovic Marko , Schmid Janine , Schubert Undine , Jarzebska Natalia , von Mässenhausen Anne , Linkermann Andreas , Schürmann Annette , Pablik Jessica , Dienemann Thomas , Evert Katja , Rodionov Roman N. , Semenova Natalia Y. , Zinserling Vsevolod A. , Gainetdinov Raul R. , Baretton Gustavo , Lindemann Dirk , Solimena Michele , Ludwig Barbara , Bornstein Stefan R. 
Published: June 2021

AbstractMetabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Here, we performed a comprehensive analysis of pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy and detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. In eleven COVID-19 patients, we examined the expression of ACE2, TMPRSS and other receptors and factors, such as DPP4, HMBG1 and NRP1, that might facilitate virus entry. Whereas 70% of the COVID-19 patients expressed ACE2 in the vasculature, only 30% displayed ACE2-expression in beta-cells. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.