bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐Instrument Observations of the Ionospheric Response to the 26 December 2019 Solar Eclipse Over Indian and Southeast Asian Longitudes
Authors: Barad R. K. , Sripathi S. , England S. L. 
Published: August 2022

AbstractHere, the impact of the 26 December 2019 solar eclipse on the equatorial and low latitude ionosphere has been investigated using ground and space‐based observations over Indian and Southeast Asian longitudes. The high‐resolution Ionosonde observations at Tirunelveli, GPS Total Electron Content (TEC) observations from a chain of GPS receivers along and across the eclipse path, TIMED‐SABER, and Ionospheric Connection Explorer (ICON) satellites were utilized to investigate the eclipse‐induced variations in electron density and thermospheric cooling. We noticed a tremendous increase and decrease in the base height of the F‐layer, resembling the nighttime Pre‐Reversal Enhancement (PRE). Near the eclipse maximum, a strong blanketing sporadic E layer was observed at Tirunelveli with a top frequency of ∼18 MHz for 1 hr and 26 min. Satellite traces (STs) and “U” shaped ionograms were noticed for the first time over Tirunelveli during eclipse maximum and end phases. The “STs” and “U” shaped traces indicate the presence of short‐period gravity waves or TID type of wave perturbations over the Indian region. A maximum of ∼5–7 TECU (30%–40%) decrease in TEC is observed on the eclipse day for iisc, hyde, and tiru stations. Periodogram analyses of TEC data showed the presence of wavelike structures with periodicities of 18–24 min for different stations. Simultaneous observations from the ICON satellite showed an increase and decrease in hmF2 and NmF2 which matches well with the ionosonde observations from Tirunelveli. The temperature profiles from TIMED‐SABER and ICON satellites showed a reduction and enhancement in the lower and upper E regions respectively.
Effects of Geologic Setting on Contaminant Transport in Deltaic Aquifers
Authors: Xu Zhongyuan , Hariharan Jayaram , Passalacqua Paola , Steel Elisabeth , Chadwick Austin , Paola Chris , Paldor Anner , Michael Holly A. 
Published: August 2022

AbstractCoastal deltaic aquifers are vulnerable to degradation from seawater intrusion, geogenic and anthropogenic contamination, and groundwater abstraction. The distribution and transport of contaminants are highly dependent on the subsurface sedimentary architecture, such as the presence of channelized features that preferentially conduct flow. Surface deposition changes in response to sea‐level rise (SLR) and sediment supply, but it remains unclear how these surface changes affect the distribution and transport of groundwater solutes in aquifers. Here, we explore the influence of SLR and sediment supply on aquifer heterogeneity and resulting effects on contaminant transport. We use realizations of subsurface heterogeneity generated by a process‐based numerical model, DeltaRCM, which simulates the evolution of a deltaic aquifer with different input sand fractions and rates of SLR. We simulate groundwater flow and solute transport through these deposits in three contamination scenarios: (a) vertical transport from widespread contamination at the land surface, (b) vertical transport from river water infiltration, and (c) lateral seawater intrusion. The simulations show that the vulnerability of deltaic aquifers to seawater intrusion correlates to sand fraction, while vertical transport of contaminants, such as widespread shallow contamination and river water infiltration, is influenced by channel stacking patterns. This analysis provides new insights into the connection between the depositional system properties and vulnerability to different modes of groundwater contamination. It also illustrates how vulnerability may vary locally within a delta due to depositional differences. Results suggest that groundwater management strategies may be improved by considering surface features, location within the delta, and the external forcings during aquifer deposition.
Molecular mechanisms underlying iron and phosphorus co-limitation responses in the nitrogen-fixing cyanobacterium Crocosphaera
Authors: Yang Nina , Lin Yu-An , Merkel Carlin A , DeMers Michelle A , Qu Ping-Ping , Webb Eric A , Fu Fei-Xue , Hutchins David A 
Published: August 2022

Abstract
In the nitrogen-limited subtropical gyres, diazotrophic cyanobacteria, including Crocosphaera, provide an essential ecosystem service by converting dinitrogen (N2) gas into ammonia to support primary production in these oligotrophic regimes. Natural gradients of phosphorus (P) and iron (Fe) availability in the low-latitude oceans constrain the biogeography and activity of diazotrophs with important implications for marine biogeochemical cycling. Much remains unknown regarding Crocosphaera’s physiological and molecular responses to multiple nutrient limitations. We cultured C. watsonii under Fe, P, and Fe/P (co)-limiting scenarios to link cellular physiology with diel gene expression and observed unique physiological and transcriptional profiles for each treatment. Counterintuitively, reduced growth and N2 fixation resource use efficiencies (RUEs) for Fe or P under P limitation were alleviated under Fe/P co-limitation. Differential gene expression analyses show that Fe/P co-limited cells employ the same responses as single-nutrient limited cells that reduce cellular nutrient requirements and increase responsiveness to environmental change including smaller cell size, protein turnover (Fe-limited), and upregulation of environmental sense-and-respond systems (P-limited). Combined, these mechanisms enhance growth and RUEs in Fe/P co-limited cells. These findings are important to our understanding of nutrient controls on N2 fixation and the implications for primary productivity and microbial dynamics in a changing ocean.
Ammonium tetrathiomolybdate triggers autophagy-dependent NRF2 activation in vascular endothelial cells
Authors: Zhang Mengling , Qiu Hongmei , Mao Lejiao , Wang Bin , Li Na , Fan Yinzhen , Weng Ping , Hu Siyao , Dong Xiaomei , Qin Xia , Chen Chengzhi , Zou Zhen , Yu Chao , Zhang Jun 
Published: August 2022

AbstractAmmonium tetrathiomolybdate (TTM) is a copper chelator in clinical trials for treatment of Wilson’s disease, tumors and other diseases. In the current study, we innovatively discovered that TTM is a novel NRF2 activator and illustrated that autophagy contributed to TTM-induced NRF2 activation. We showed that TTM treatment promoted NRF2 nuclear translocation and upregulated transcription level of NRF2 target genes includingHMOX1,GCLM, andSLC7A11in vascular endothelial cells (HUVECs). Moreover, NRF2 deficiency directly hindered TTM-mediated antioxidative effects. Followingly, we revealed that overexpression of KEAP1, a negative regulator of NRF2, significantly repressed NRF2 activation induced by TTM. Further mutation analysis revealed that KEAP1 Cys151 is a major sensor responsible for TTM-initiated NRF2 signaling, suggesting that KEAP1 is involved in TTM-mediated NRF2 activation. Notably, we found that TTM can trigger autophagy as evidenced by accumulation of autophagosomes, elevation of LC3BI-II/I, increase of LC3 puncta and activation of AMPK/mTOR/ULK1 pathway. Autophagic flux assay indicated that TTM significantly enhanced autophagic flux in HUVECs. Inhibition of autophagy with knockout of autophagy key geneATG5resulted in suppression of TTM-induced NRF2 activation. TTM also induced phosphorylation of autophagy receptor SQSTM1 at Ser349, while SQSTM1-deficiency inhibited KEAP1 degradation and blocked NRF2 signaling pathway, suggesting that TTM-induced NRF2 activation is autophagy dependent. As the novel NRF2 activator, TTM protected against sodium arsenite (NaAsO2)-induced oxidative stress and cell death, while NRF2 deficiency weakened TTM antioxidative effects. Finally, we showed that autophagy-dependent NRF2 activation contributed to the protective effects of TTM against NaAsO2-induced oxidative injury, because ofATG5orSQSTM1knockout aggravated NaAsO2-induced elevation of HMOX1, cleaved PARP and γH2AX. Taken together, our findings highlight copper chelator TTM is a novel autophagy-dependent NRF2 activator and shed a new light on the cure for oxidative damage-related diseases.
Zeb1 sustains hematopoietic stem cell functions by suppressing mitofusin-2-mediated mitochondrial fusion
Authors: Zhang Kai , Zhao Huifang , Sheng Yaru , Chen Xinyu , Xu Penghui , Wang Jinming , Ji Zhongzhong , He Yuman , Gao Wei-Qiang , Zhu Helen He 
Published: August 2022

AbstractMetabolic status is essential in maintaining normal functions of hematopoietic stem cells (HSCs). However, how the dynamic of the mitochondrion, as a central organelle in metabolism, is molecularly regulated to orchestrate metabolism and HSC stemness remains to be elucidated. Here, we focus on the role of Zeb1, a well-characterized epithelial-to-mesenchymal transition (EMT) inducer which has been demonstrated to confer stem-cell-like characteristics in multiple cancer types in stemness regulation of HSCs. Using a Zeb1-tdTomato reporter mouse model, we find that Zeb1+Lin−Sca-1+c-Kit+ cells (Zeb1+-LSKs) represent a subset of functional long-term HSCs. Zeb1+LSKs exhibit a reduced reactive oxygen species (ROS) level, low mitochondrial mass, low mitochondrial membrane potential (MMP), and particularly small, round fragmented mitochondria. Of note, ectopic expression of Zeb1 leads to a fragmented mitochondrial morphology with a low mitochondrial metabolic status in EML cells. In addition, Zeb1-knockout (Zeb1-KO) LSKs from fetal liver display an exhausted stem-cell activity. Zeb1 deficiency results in elongated and tubulated mitochondria with increased mitochondrial mass, elevated MMP, and higher ROS production. Mechanistically, Zeb1 acts as a transcriptional suppressor on the key mitochondrial-fusion protein Mitofusin-2 (encoded by Mfn2). We highlight an important role of Zeb1 in the regulation of mitochondrial morphology in HSC and the metabolic control of HSC stemness by repressing Mfn2-mediated mitochondrial fusion.
Complete classification of steerability under local filters and its relation with measurement incompatibility
Authors: Ku Huan-Yu , Hsieh Chung-Yun , Chen Shin-Liang , Chen Yueh-Nan , Budroni Costantino 
Published: August 2022

AbstractQuantum steering is a central resource for one-sided device-independent quantum information. It is manipulated via one-way local operations and classical communication, such as local filtering on the trusted party. Here, we provide a necessary and sufficient condition for a steering assemblage to be transformable into another via local filtering. We characterize the equivalence classes with respect to filters in terms of the steering equivalent observables (SEO), first proposed to connect the problem of steerability and measurement incompatibility. We provide an efficient method to compute the extractable steerability that is maximal via local filters and show that it coincides with the incompatibility of the SEO. Moreover, we show that there always exists a bipartite state that provides an assemblage with steerability equal to the incompatibility of the measurements on the untrusted party. Finally, we investigate the optimal success probability and rates for transformation protocols (distillation and dilution) in the single-shot scenario together with examples.
Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids
Authors: Song Hanbing , Bucher Simon , Rosenberg Katherine , Tsui Margaret , Burhan Deviana , Hoffman Daniel , Cho Soo-Jin , Rangaswami Arun , Breese Marcus , Leung Stanley , Ventura María V. Pons , Sweet-Cordero E. Alejandro , Huang Franklin W. , Nijagal Amar , Wang Bruce 
Published: August 2022

AbstractPediatric hepatoblastoma is the most common primary liver cancer in infants and children. Studies of hepatoblastoma that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, hepatoblastoma tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we use single-cell transcriptomic techniques to analyze resected human pediatric hepatoblastoma specimens, and identify five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease. Notably, patient-derived hepatoblastoma spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. In this work, we define hepatoblastoma tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.
Experimental demonstration of adversarial examples in learning topological phases
Authors: Zhang Huili , Jiang Si , Wang Xin , Zhang Wengang , Huang Xianzhi , Ouyang Xiaolong , Yu Yefei , Liu Yanqing , Deng Dong-Ling , Duan L.-M. 
Published: August 2022

AbstractClassification and identification of different phases and the transitions between them is a central task in condensed matter physics. Machine learning, which has achieved dramatic success in a wide range of applications, holds the promise to bring unprecedented perspectives for this challenging task. However, despite the exciting progress made along this direction, the reliability of machine-learning approaches in experimental settings demands further investigation. Here, with the nitrogen-vacancy center platform, we report a proof-of-principle experimental demonstration of adversarial examples in learning topological phases. We show that the experimental noises are more likely to act as adversarial perturbations when a larger percentage of the input data are dropped or unavailable for the neural network-based classifiers. We experimentally implement adversarial examples which can deceive the phase classifier with a high confidence, while keeping the topological properties of the simulated Hopf insulators unchanged. Our results explicitly showcase the crucial vulnerability aspect of applying machine learning techniques in experiments to classify phases of matter, which can benefit future studies in this interdisciplinary field.
Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance
Authors: Tye Mark A. , Payne N. Connor , Johansson Catrine , Singh Kritika , Santos Sofia A. , Fagbami Lọla , Pant Akansha , Sylvester Kayla , Luth Madeline R. , Marques Sofia , Whitman Malcolm , Mota Maria M. , Winzeler Elizabeth A. , Lukens Amanda K. , Derbyshire Emily R. , Oppermann Udo , Wirth Dyann F. , Mazitschek Ralph 
Published: August 2022

AbstractThe development of next-generation antimalarials that are efficacious against the human liver and asexual blood stages is recognized as one of the world’s most pressing public health challenges. In recent years, aminoacyl-tRNA synthetases, including prolyl-tRNA synthetase, have emerged as attractive targets for malaria chemotherapy. We describe the development of a single-step biochemical assay for Plasmodium and human prolyl-tRNA synthetases that overcomes critical limitations of existing technologies and enables quantitative inhibitor profiling with high sensitivity and flexibility. Supported by this assay platform and co-crystal structures of representative inhibitor-target complexes, we develop a set of high-affinity prolyl-tRNA synthetase inhibitors, including previously elusive aminoacyl-tRNA synthetase triple-site ligands that simultaneously engage all three substrate-binding pockets. Several compounds exhibit potent dual-stage activity against Plasmodium parasites and display good cellular host selectivity. Our data inform the inhibitor requirements to overcome existing resistance mechanisms and establish a path for rational development of prolyl-tRNA synthetase-targeted anti-malarial therapies.
Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide
Authors: Hansen Nikolaj Lervad , Kjaerulff Louise , Heck Quinn Kalby , Forman Victor , Staerk Dan , Møller Birger Lindberg , Andersen-Ranberg Johan 
Published: August 2022

AbstractThe diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b5 (Twcytb5-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.
Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis
Authors: Tian Tian , Wang Yong-Jiang , Huang Jian-Ping , Li Jie , Xu Bingyan , Chen Yin , Wang Li , Yang Jing , Yan Yijun , Huang Sheng-Xiong 
Published: August 2022

AbstractTropane alkaloids such as hyoscyamine and cocaine are of importance in medicinal uses. Only recently has the hyoscyamine biosynthetic machinery become complete. However, the cocaine biosynthesis pathway remains only partially elucidated. Here we characterize polyketide synthases required for generating 3-oxo-glutaric acid from malonyl-CoA in cocaine biosynthetic route. Structural analysis shows that these two polyketide synthases adopt distinctly different active site architecture to catalyze the same reaction as pyrrolidine ketide synthase in hyoscyamine biosynthesis, revealing an unusual parallel/convergent evolution of biochemical function in homologous enzymes. Further phylogenetic analysis suggests lineage-specific acquisition of polyketide synthases required for tropane alkaloid biosynthesis in Erythroxylaceae and Solanaceae species, respectively. Overall, our work elucidates not only a key unknown step in cocaine biosynthesis pathway but also, more importantly, structural and biochemical basis for independent recruitment of polyketide synthases in tropane alkaloid biosynthesis, thus broadening the understanding of conservation and innovation of biosynthetic catalysts.
Methylation risk scores are associated with a collection of phenotypes within electronic health record systems
Authors: Thompson Mike , Hill Brian L. , Rakocz Nadav , Chiang Jeffrey N. , Geschwind Daniel , Sankararaman Sriram , Hofer Ira , Cannesson Maxime , Zaitlen Noah , Halperin Eran 
Published: August 2022

AbstractInference of clinical phenotypes is a fundamental task in precision medicine, and has therefore been heavily investigated in recent years in the context of electronic health records (EHR) using a large arsenal of machine learning techniques, as well as in the context of genetics using polygenic risk scores (PRS). In this work, we considered the epigenetic analog of PRS, methylation risk scores (MRS), a linear combination of methylation states. We measured methylation across a large cohort (n = 831) of diverse samples in the UCLA Health biobank, for which both genetic and complete EHR data are available. We constructed MRS for 607 phenotypes spanning diagnoses, clinical lab tests, and medication prescriptions. When added to a baseline set of predictive features, MRS significantly improved the imputation of 139 outcomes, whereas the PRS improved only 22 (median improvement for methylation 10.74%, 141.52%, and 15.46% in medications, labs, and diagnosis codes, respectively, whereas genotypes only improved the labs at a median increase of 18.42%). We added significant MRS to state-of-the-art EHR imputation methods that leverage the entire set of medical records, and found that including MRS as a medical feature in the algorithm significantly improves EHR imputation in 37% of lab tests examined (median R2 increase 47.6%). Finally, we replicated several MRS in multiple external studies of methylation (minimum p-value of 2.72 × 10−7) and replicated 22 of 30 tested MRS internally in two separate cohorts of different ethnicity. Our publicly available results and weights show promise for methylation risk scores as clinical and scientific tools.
Wildfire-dependent changes in soil microbiome diversity and function
Authors: Nelson Amelia R. , Narrowe Adrienne B. , Rhoades Charles C. , Fegel Timothy S. , Daly Rebecca A. , Roth Holly K. , Chu Rosalie K. , Amundson Kaela K. , Young Robert B. , Steindorff Andrei S. , Mondo Stephen J. , Grigoriev Igor V. , Salamov Asaf , Borch Thomas , Wilkins Michael J. 
Published: August 2022

AbstractForest soil microbiomes have crucial roles in carbon storage, biogeochemical cycling and rhizosphere processes. Wildfire season length, and the frequency and size of severe fires have increased owing to climate change. Fires affect ecosystem recovery and modify soil microbiomes and microbially mediated biogeochemical processes. To study wildfire-dependent changes in soil microbiomes, we characterized functional shifts in the soil microbiota (bacteria, fungi and viruses) across burn severity gradients (low, moderate and high severity) 1 yr post fire in coniferous forests in Colorado and Wyoming, USA. We found severity-dependent increases of Actinobacteria encoding genes for heat resistance, fast growth, and pyrogenic carbon utilization that might enhance post-fire survival. We report that increased burn severity led to the loss of ectomycorrhizal fungi and less tolerant microbial taxa. Viruses remained active in post-fire soils and probably influenced carbon cycling and biogeochemistry via turnover of biomass and ecosystem-relevant auxiliary metabolic genes. Our genome-resolved analyses link post-fire soil microbial taxonomy to functions and reveal the complexity of post-fire soil microbiome activity.