bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupled Climate Responses to Recent Australian Wildfire and COVID‐19 Emissions Anomalies Estimated in CESM2
Authors: Fasullo J. T. , Rosenbloom N. , Buchholz R. R. , Danabasoglu G. , Lawrence D. M. , Lamarque J.‐F. 
Published: July 2021

AbstractMultiple 50‐member ensemble simulations with the Community Earth System Model version 2 are performed to estimate the coupled climate responses to the 2019–2020 Australian wildfires and COVID‐19 pandemic policies. The climate response to the pandemic is found to be weak generally, with global‐mean net top‐of‐atmosphere radiative anomalies of +0.23 ± 0.14 W m−2 driving a gradual global warming of 0.05 ± 0.04 K by the end of 2022. While regional anomalies are detectable in aerosol burdens and clear‐sky radiation, few significant anomalies exist in other fields due to internal variability. In contrast, the simulated response to Australian wildfires is a strong and rapid cooling, peaking globally at −0.95 ± 0.15 W m−2 in late 2019 with a global cooling of 0.06 ± 0.04 K by mid‐2020. Transport of fire aerosols throughout the Southern Hemisphere increases albedo and drives a strong interhemispheric radiative contrast, with simulated responses that are consistent generally with those to a Southern Hemisphere volcanic eruption.
6,000‐Year Reconstruction of Modified Circumpolar Deep Water Intrusion and Its Effects on Sea Ice and Penguin in the Ross Sea
Authors: Xu Q. B. , Yang L. J. , Gao Y. S. , Sun L. G. , Xie Z. Q. 
Published: July 2021

AbstractThe Ross Sea has the world's largest marine protected area. Modified Circumpolar Deep Water (MCDW) has significant effects on physical and biological processes in the Ross Sea. Totally 13 penguin ornithogenic sediment profiles were collected from Inexpressible Island, Ross Sea, and the Cd/P ratios were used as a proxy of MCDW intrusion, enabling to reconstruct the variability of MCDW intrusion into the Ross Sea during the past 6,000 years. During the intervals of ∼0.7–1.6 and ∼2.8–6.0 kyr BP, enhanced MCDW intrusion increased the heat supply which warmed the surface water and reduced the coastal sea ice concentration. By contrast, reduced MCDW intrusion during ∼1.6–2.8 kyr BP caused a decrease in the penguin population via restricting food supply and/or increasing sea ice concentration. Thus, changes in MCDW were responsible for driving millennial changes in sea ice and penguin population in the Ross Sea.
ARTEMIS Observations of Lunar Nightside Surface Potentials in the Magnetotail Lobes: Evidence for Micrometeoroid Impact Charging
Authors: Poppe A. R. , Xu S. , Liuzzo L. , Halekas J. S. , Harada Y. 
Published: July 2021

AbstractThe Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moon's Interaction with the Sun mission observes anomalously low lunar nightside surface potentials while in the terrestrial magnetotail lobes. Observed potential magnitudes are between 15% and 40% that expected from ambient tail‐plasma charging, are highly concentrated on the lunar dawn hemisphere, and are correlated with low ambient plasma densities. These characteristics suggest an additional, highly asymmetric source of cold current to the lunar surface. Given these characteristics, we identify micrometeoroid impact‐generated plasmas as the likely source of this additional current. Using laboratory measurements of impact charge yields and models of the micrometeoroid flux to the Moon constrained by in situ measurements, we show that currents due to micrometeoroid impact plasmas have the necessary magnitude and spatial distribution to explain the observed surface potential measurements. Micrometeoroid impact‐generated currents may contribute to surface charging at airless bodies with intense micrometeoroid bombardment and/or low ambient plasma densities.
Physical Origin of Recurrent Magnetic Dipolarization Events in Saturn’s Equatorial Plasma Sheet
Authors: Cowley S. W. H. , Provan G. 
Published: July 2021

AbstractWe consider the physical origin of reconnection‐related events in Saturn’s equatorial current sheet revealed by Cassini, specifically the dipolarization events discussed by Yao et al. (https://doi.org/10.1029/2018JA025837) that recur close to the ∼10.7 h planetary period oscillation (PPO) period. We argue that Yao et al.’s preferred recurrence explanation in terms of complete rotations of dipolarized field/current structures around the planet at close to the PPO period is highly implausible. All‐mission observations of ion flows at relevant radial ranges ∼20–30 Saturn radii are essentially invariably sub‐corotational, including reconnection‐related hot ion injections, thus requiring implausible structure propagation at significant speeds through the plasma. We further show their assertion that the nightside events occur at PPO phases unfavorable for reconnection is incorrect. These events instead occur under PPO conditions associated with outward radial plasma displacement and/or a thinning plasma sheet with falling colatitudinal field, shown previously to be optimal for modulated reconnection bursts leading to dipolarizations and plasmoids. We instead suggest these events are related to well‐documented Vasyliunas cycle disturbances, when two reconnection episodes happen to be triggered at similar favorable PPO phases on successive PPO cycles. Yao et al.’s dayside events do occur at phases unfavorable for recurrent reconnection, but may then simply be an effect of periodic field/plasma modulations during the regular PPO cycle combined with subcorotating small‐scale structures often present in the plasma sheet. Both dayside and nightside events can thus be understood within existing knowledge of PPO modulations of the structure and dynamics of Saturn’s equatorial current sheet.
Impacts of the Eruption of Mount Pinatubo on Surface Temperatures and Precipitation Forecasts With the NASA GEOS Subseasonal‐to‐Seasonal System
Authors: Aquila Valentina , Baldwin Colleen , Mukherjee Nikita , Hackert Eric , Li Feng , Marshak Jelena , Molod Andrea , Pawson Steven 
Published: July 2021

AbstractA contemporary seasonal forecasting system is used to study the impacts of a volcanic sulfate injection into the stratosphere on the seasonal forecasts for surface temperatures, the El Niño Southern Oscillation (ENSO), and precipitation. The focus is a case study of the June 1991 eruption of Mt. Pinatubo, Philippines and the period from July 1991 to February 1992. Version 2 of the Goddard Earth Observing System (GEOS) subseasonal‐to‐seasonal (S2S) forecasting system is used in this study. GEOS‐S2S includes the GOddard Chemistry, Aerosols, Radiation and Transport (GOCART) aerosol module, which allows to prognostically simulate aerosol distributions. GOCART is coupled to the radiation and cloud modules to include the impact of the eruption on forecasted radiation and precipitation. The coupled GEOS‐S2S system was initialized in May 1991 with fields based on observations to produce ten‐member 9‐month forecasts with and without the volcanic sulfur injection. The results of these ensemble experiments demonstrate that including Mt. Pinatubo in seasonal forecasts would improve the forecasts of the 1991–1992 global mean temperature and precipitation but worsen the forecast of ENSO by strengthening of El Niño beyond what showed in observations. Most significant changes in the forecasts of temperatures and precipitation are limited to the tropics. The only land area where the inclusion of Pinatubo significantly lowered the forecasted precipitation is tropical Africa.
Experimental Investigation of Physical Leaky Barrier Design Implications on Juvenile Rainbow Trout (Oncorhynchus mykiss) Movement
Authors: Müller Stephanie , Wilson Catherine A. M. E. , Ouro Pablo , Cable Joanne 
Published: July 2021

AbstractRivers have been subject to the construction of numerous small‐scale anthropogenic structures, causing the alteration and fragmentation of habitats. Despite their impact on fish habitat selection, migration, and swimming performance, more hydraulic structures are being added to riverine systems. These mainly have the purpose of harnessing renewable energy or mitigating the impact of flooding, as in the case of leaky barriers that are widely used for natural flood management. By providing a sustainable and cost‐effective supplement to traditional hard engineering flood risk management methods, these channel‐spanning wooden barriers are constructed using sustainable, local materials, intended to slow down surface water and groundwater flow, reduce flood peaks, and attenuate the flow reaching downstream communities. Despite their increasing popularity, little is known about the design implications on fish movement or hydrodynamics. Using scaled laboratory flume experiments we investigate how the physical design of four leaky barriers varying in porosity, length, provision of overhead cover, and color, impact on fish movement and spatial usage, and the channel hydrodynamics. Our fish behavioral analysis reveals that juvenile rainbow trout (Oncorhynchus mykiss) movement reduces with barrier presence. Upstream passage increases with barrier color but not cover, for shorter rather than longer leaky barriers, and for a non‐porous barrier compared to its porous counterpart. Barrier‐specific flow alterations appear to play a secondary role compared to barrier color. Our study showed that physical barrier design and leaky barrier presence alter fish movement, and therefore care needs to be taken during the design of such natural flood management structures.
DiLFM: an artifact-suppressed and noise-robust light-field microscopy through dictionary learning
Authors: Zhang Yuanlong , Xiong Bo , Zhang Yi , Lu Zhi , Wu Jiamin , Dai Qionghai 
Published: July 2021

AbstractLight field microscopy (LFM) has been widely used for recording 3D biological dynamics at camera frame rate. However, LFM suffers from artifact contaminations due to the illness of the reconstruction problem via naïve Richardson–Lucy (RL) deconvolution. Moreover, the performance of LFM significantly dropped in low-light conditions due to the absence of sample priors. In this paper, we thoroughly analyze different kinds of artifacts and present a new LFM technique termed dictionary LFM (DiLFM) that substantially suppresses various kinds of reconstruction artifacts and improves the noise robustness with an over-complete dictionary. We demonstrate artifact-suppressed reconstructions in scattering samples such as Drosophila embryos and brains. Furthermore, we show our DiLFM can achieve robust blood cell counting in noisy conditions by imaging blood cell dynamic at 100 Hz and unveil more neurons in whole-brain calcium recording of zebrafish with low illumination power in vivo.
Photonic-dispersion neural networks for inverse scattering problems
Authors: Li Tongyu , Chen Ang , Fan Lingjie , Zheng Minjia , Wang Jiajun , Lu Guopeng , Zhao Maoxiong , Cheng Xinbin , Li Wei , Liu Xiaohan , Yin Haiwei , Shi Lei , Zi Jian 
Published: July 2021

AbstractInferring the properties of a scattering objective by analyzing the optical far-field responses within the framework of inverse problems is of great practical significance. However, it still faces major challenges when the parameter range is growing and involves inevitable experimental noises. Here, we propose a solving strategy containing robust neural-networks-based algorithms and informative photonic dispersions to overcome such challenges for a sort of inverse scattering problem—reconstructing grating profiles. Using two typical neural networks, forward-mapping type and inverse-mapping type, we reconstruct grating profiles whose geometric features span hundreds of nanometers with nanometric sensitivity and several seconds of time consumption. A forward-mapping neural network with a parameters-to-point architecture especially stands out in generating analytical photonic dispersions accurately, featured by sharp Fano-shaped spectra. Meanwhile, to implement the strategy experimentally, a Fourier-optics-based angle-resolved imaging spectroscopy with an all-fixed light path is developed to measure the dispersions by a single shot, acquiring adequate information. Our forward-mapping algorithm can enable real-time comparisons between robust predictions and experimental data with actual noises, showing an excellent linear correlation (R2 > 0.982) with the measurements of atomic force microscopy. Our work provides a new strategy for reconstructing grating profiles in inverse scattering problems.
CRISPR screening identifies CDK12 as a conservative vulnerability of prostate cancer
Authors: Lei Hanqi , Wang Zifeng , Jiang Donggen , Liu Fang , Liu Meiling , Lei Xinxing , Yang Yafei , He Bin , Yan Min , Huang Hai , Liu Quentin , Pang Jun 
Published: July 2021

AbstractAndrogen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. Thus, a better understanding of the critical dependencies of PCa may enable more feasible therapeutic approaches to the dilemma. We performed a kinome-scale CRISPR/Cas9 screen and identified cyclin-dependent kinase 12 (CDK12) as being conservatively required for PCa cell survival. Suppression of CDK12 by the covalent inhibitor THZ531 led to an obvious anti-PCa effect. Mechanistically, THZ531 downregulated AR signaling and preferentially repressed a distinct class of CDK12 inhibition-sensitive transcripts (CDK12-ISTs), including prostate lineage-specific genes, and contributed to cellular survival processes. Integration of the super-enhancer (SE) landscape and CDK12-ISTs indicated a group of potential PCa oncogenes, further conferring the sensitivity of PCa cells to CDK12 inhibition. Importantly, THZ531 strikingly synergized with multiple AR antagonists. The synergistic effect may be driven by attenuated H3K27ac signaling on AR targets and an intensive SE-associated apoptosis pathway. In conclusion, we highlight the validity of CDK12 as a druggable target in PCa. The synergy of THZ531 and AR antagonists suggests a potential combination therapy for PCa.
Dynamic BH3 profiling identifies active BH3 mimetic combinations in non-small cell lung cancer
Authors: Potter Danielle S. , Du Ruochen , Bhola Patrick , Bueno Raphael , Letai Anthony 
Published: July 2021

AbstractConventional chemotherapy is still of great utility in oncology and rationally constructing combinations with it remains a top priority. Drug-induced mitochondrial apoptotic priming, measured by dynamic BH3 profiling (DBP), has been shown in multiple cancers to identify drugs that promote apoptosis in vivo. We therefore hypothesized that we could use DBP to identify drugs that would render cancers more sensitive to conventional chemotherapy. We found that targeted agents that increased priming of non-small cell lung cancer (NSCLC) tumor cells resulted in increased sensitivity to chemotherapy in vitro. To assess whether targeted agents that increase priming might enhance the efficacy of cytotoxic agents in vivo as well, we carried out an efficacy study in a PC9 xenograft mouse model. The BH3 mimetic navitoclax, which antagonizes BCL-xL, BCL-w, and BCL-2, consistently primed NSCLC tumors in vitro and in vivo. The BH3 mimetic venetoclax, which electively antagonizes BCL-2, did not. Combining navitoclax with etoposide significantly reduced tumor burden compared to either single agent, while adding venetoclax to etoposide had no effect on tumor burden. Next, we assessed priming of primary patient NSCLC tumor cells on drugs from a clinically relevant oncology combination screen (CROCS). Results confirmed for the first time the utility of BCL-xL inhibition by navitoclax in priming primary NSCLC tumor cells and identified combinations that primed further. This is a demonstration of the principle that DBP can be used as a functional precision medicine tool to rationally construct combination drug regimens that include BH3 mimetics in solid tumors like NSCLC.
Retinoblastoma from human stem cell-derived retinal organoids
Authors: Norrie Jackie L. , Nityanandam Anjana , Lai Karen , Chen Xiang , Wilson Matthew , Stewart Elizabeth , Griffiths Lyra , Jin Hongjian , Wu Gang , Orr Brent , Tran Quynh , Allen Sariah , Reilly Colleen , Zhou Xin , Zhang Jiakun , Newman Kyle , Johnson Dianna , Brennan Rachel , Dyer Michael A. 
Published: July 2021

AbstractRetinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. Genetically engineered mouse models of retinoblastoma share some similarities with human retinoblastoma but there are differences in their cellular differentiation. To develop a laboratory model of human retinoblastoma formation, we make induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. Each of the stem cell lines is validated, characterized and then differentiated into retina using a 3-dimensional organoid culture system. After 45 days in culture, the retinal organoids are dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs have molecular, cellular and genomic features indistinguishable from human retinoblastomas. This model of human cancer based on patient-derived iPSCs with germline cancer predisposing mutations provides valuable insights into the cellular origins of this debilitating childhood disease as well as the mechanism of tumorigenesis following RB1 gene inactivation.
Chloride sensing by WNK1 regulates NLRP3 inflammasome activation and pyroptosis
Authors: Mayes-Hopfinger Lindsey , Enache Aura , Xie Jian , Huang Chou-Long , Köchl Robert , Tybulewicz Victor L. J. , Fernandes-Alnemri Teresa , Alnemri Emad S. 
Published: July 2021

AbstractThe NLRP3 inflammasome mediates the production of proinflammatory cytokines and initiates inflammatory cell death. Although NLRP3 is essential for innate immunity, aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases. Understanding the pathways that control NLRP3 activation will help develop strategies to treat these diseases. Here we identify WNK1 as a negative regulator of the NLRP3 inflammasome. Macrophages deficient in WNK1 protein or kinase activity have increased NLRP3 activation and pyroptosis compared with control macrophages. Mice with conditional knockout of WNK1 in macrophages have increased IL-1β production in response to NLRP3 stimulation compared with control mice. Mechanistically, WNK1 tempers NLRP3 activation by balancing intracellular Cl– and K+ concentrations during NLRP3 activation. Collectively, this work shows that the WNK1 pathway has a critical function in suppressing NLRP3 activation and suggests that pharmacological inhibition of this pathway to treat hypertension might have negative clinical implications.
Extracellular vesicles and exosomes generated from cystic renal epithelial cells promote cyst growth in autosomal dominant polycystic kidney disease
Authors: Ding Hao , Li Linda Xiaoyan , Harris Peter C. , Yang Junwei , Li Xiaogang 
Published: July 2021

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is caused by germline mutations of PKD1 or PKD2 on one allele and a somatic mutation inactivating the remaining normal allele. However, if and how null ADPKD gene renal epithelial cells affect the biology and function of neighboring cells, including heterozygous renal epithelial cells, fibroblasts and macrophages during cyst initiation and expansion remains unknown. Here we address this question with a “cystic extracellular vesicles/exosomes theory”. We show that cystic cell derived extracellular vesicles and urinary exosomes derived from ADPKD patients promote cyst growth in Pkd1 mutant kidneys and in 3D cultures. This is achieved by: 1) downregulation of Pkd1 gene expression and upregulation of specific miRNAs, resulting in the activation of PKD associated signaling pathways in recipient renal epithelial cells and tissues; 2) the activation of fibroblasts; and 3) the induction of cytokine expression and the recruitment of macrophages to increase renal inflammation in cystic kidneys. Inhibition of exosome biogenesis/release with GW4869 significantly delays cyst growth in aggressive and milder ADPKD mouse models, suggesting that targeting exosome secretion has therapeutic potential for ADPKD.
Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets
Authors: Lee Jeong Seok , Koh June-Young , Yi Kijong , Kim Young-Il , Park Su-Jin , Kim Eun-Ha , Kim Se-Mi , Park Sung Ho , Ju Young Seok , Choi Young Ki , Park Su-Hyung 
Published: July 2021

AbstractFew studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.
Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome
Authors: Garcia Patricia , Fernandez-Hernandez Rita , Cuadrado Ana , Coca Ignacio , Gomez Antonio , Maqueda Maria , Latorre-Pellicer Ana , Puisac Beatriz , Ramos Feliciano J. , Sandoval Juan , Esteller Manel , Mosquera Jose Luis , Rodriguez Jairo , Pié J. , Losada Ana , Queralt Ethel 
Published: July 2021

AbstractCornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not understood. In addition to its canonical role in sister chromatid cohesion, cohesin is implicated in the spatial organization of the genome. Here, we investigate the transcriptome of CdLS patient-derived primary fibroblasts and observe the downregulation of genes involved in development and system skeletal organization, providing a link to the developmental alterations and limb abnormalities characteristic of CdLS patients. Genome-wide distribution studies demonstrate a global reduction of NIPBL at the NIPBL-associated high GC content regions in CdLS-derived cells. In addition, cohesin accumulates at NIPBL-occupied sites at CpG islands potentially due to reduced cohesin translocation along chromosomes, and fewer cohesin peaks colocalize with CTCF.