bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pacific Waters Pathways and Vertical Mixing in the CESM1‐LE: Implication for Mixed Layer Depth Evolution and Sea Ice Mass Balance in the Canada Basin
Authors: Lavoie Juliette , Tremblay Bruno , Rosenblum Erica 
Published: January 2022

AbstractWe compare the vertical hydrography of the Community Earth System Model Large Ensemble (CESM1‐LE) with observations from two specific periods: the Arctic Ice Dynamics Joint Experiment (AIDJEX; 1975–1976) and Ice‐Tethered Profilers (ITP; 2004–2018). A comparison between simulated and observed salinity and potential temperature profiles highlights two key model biases in all ensemble members: (a) an absence of Pacific Waters in the water column and (b) a slight deepening of the May mixed layer contrary to observations, which show a large reduction in the mixed‐layer depth and an increase in stratification over the same time period. We examine processes controlling the sea ice mass balance using a one‐dimensional vertical heat budget in the light of the model limitations implied by these two biases. Results indicate that remnant solar heat trapped beneath the halocline is mostly ventilated to the surface by mixing before the following melt season. Furthermore, we find that vertical advection associated with Ekman pumping has only a small effect on the vertical heat transport, even in early fall when the winds are strong and the pack ice is weak. Lastly, we estimate the impact of the missing Pacific Waters at 0.40 m of reduced winter ice growth.
REWTCrunch: A Modeling Framework for Vegetation Induced Reactive Zone Processes in the Critical Zone
Authors: Roque‐Malo Susana , Druhan Jennifer L. , Kumar Praveen 
Published: January 2022

AbstractVegetation optimizes its geochemical environment for resource management via root exudation. We refer to the soil zone where biogeochemical behavior is significantly influenced, directly or indirectly, by root processes as the vegetation induced reactive zone (VIRZ). Root exudates react with VIRZ soil substrates creating temporally variable chemical environments through depth that extend below the rooting zone, impacting weathering, and releasing solutes and gases. We present a new framework, REWTCrunch, to capture VIRZ dynamics by integrating three modeling advances: the multicomponent reactive transport model CrunchFlow, the root exudation model REWT, and the multilayer canopy‐root ecohydrologic model MLCan. REWTCrunch's high‐resolution, process‐based simulation of root exudation, and the transport and transformation of carbon (C) and nutrients according to mass‐balanced and charge‐balanced reaction networks gives new insight into vertically resolved root‐soil‐microbe‐water interactions and their influence on solute fluxes at a daily timescale. We benchmark REWT and CrunchFlow, illustrate coupling mechanisms, and present REWTCrunch simulations for an agricultural site in the US Midwest. Results demonstrate root‐sourced reactive C can augment or reduce solute concentrations in the soil by several orders of magnitude. Silicate weathering products illustrate after‐harvest effects of plant C inputs in leaching patterns. Calcium simulations reveal the development of a stable weathering front. Aluminum concentrations are particularly responsive to root‐sourced reactivity, and analysis of leaching concentration versus leaching flux indicates hysteresis behavior. REWTCrunch significant improves our ability to simulate the link between root processes and soil biogeochemistry, thereby filling an important gap in the numerical simulation of root processes, weathering, and long‐term soil health.
China's Terrestrial Carbon Sink Over 2010–2015 Constrained by Satellite Observations of Atmospheric CO2 and Land Surface Variables
Authors: He Wei , Jiang Fei , Wu Mousong , Ju Weimin , Scholze Marko , Chen Jing M. , Byrne Brendan , Liu Junjie , Wang Hengmao , Wang Jun , Wang Songhan , Zhou Yanlian , Zhang Chunhua , Nguyen Ngoc Tu , Shen Yang , Chen Zhi 
Published: January 2022

AbstractThe magnitude and distribution of China's terrestrial carbon sink remain uncertain due to insufficient constraints at large scales, whereby satellite data offer great potential for reducing the uncertainty. Here, we present two carbon sink estimates for China constrained either by satellite CO2 column concentrations (XCO2) within the Global Carbon Assimilation System or by remotely sensed soil moisture and Fraction of Absorbed Photosynthetically Active Radiation (FAPAR) in addition to in situ CO2 observations within the Carbon Cycle Data Assimilation System. They point to a moderate size of carbon sinks of 0.34 ± 0.14 (mean ± unc.) and 0.43 ± 0.09 PgC/yr during 2010–2015, which are supported by an inventory‐based estimate for forest and soil carbon sink (0.26 PgC/yr) and fall in the range of contemporary ensemble atmospheric inversions (0.25–0.48 PgC/yr). They also agree reasonably well on interannual variations, which reflect the carbon sink anomalies induced by regional droughts in southwest China. Furthermore, their spatial distributions are broadly consistent that of the forest inventory‐based estimate, indicating that the largest carbon sinks locate in central and eastern China. Their estimates for forest carbon sink coincide fairly well with the inventory‐based estimate across different regions, especially when aggregated to the north and south of China. Although enhanced recently by afforestation, China's carbon sink was also significantly weakened by regional droughts, which were often not fully represented in previous in situ CO2‐based inversions due to insufficient observations. Our results suggest that satellite‐based atmospheric CO2 and land surface observations are vital in characterizing terrestrial net carbon fluxes at regional scales.
Hydrological Basis of Different Budyko Equations: The Spatial Variability of Available Water for Evaporation
Authors: Yao Lili , Wang Dingbao 
Published: January 2022

AbstractThe available water for evaporation within a catchment is spatially variable. However, how the spatial variability of available water affects mean annual evaporation is not fully understood. For a specific catchment, a suitable distribution function defined for non‐negative random variables can be determined through statistical methods to represent the spatial variability of the available water when the point‐scale data are available. This article proposes that the distribution function representing the spatial variability of available water for evaporation determines the functional form of Budyko equation based on the one‐stage precipitation partitioning concept. Specifically, the available water for evaporation following a single‐parameter distribution function leads to a deterministic Budyko equation; whereas a two‐parameter distribution function of available water for evaporation leads to a single‐parameter Budyko equation. We identified the property of distribution function for symmetric Budyko equation, which suggests that precipitation partitioning and energy partitioning in the hydrological cycle follow the same functional form with respect to aridity index and humidity index, respectively. The lower bound of Budyko curve is explained as a result of probable distributions of available water for evaporation due to catchment co‐evolution.
Duplex DNA and BLM regulate gate opening by the human TopoIIIα-RMI1-RMI2 complex
Authors: Bakx Julia A. M. , Biebricher Andreas S. , King Graeme A. , Christodoulis Panagiotis , Sarlós Kata , Bizard Anna H. , Hickson Ian D. , Wuite Gijs J. L. , Peterman Erwin J. G. 
Published: January 2022

AbstractTopoisomerase IIIα is a type 1A topoisomerase that forms a complex with RMI1 and RMI2 called TRR in human cells. TRR plays an essential role in resolving DNA replication and recombination intermediates, often alongside the helicase BLM. While the TRR catalytic cycle is known to involve a protein-mediated single-stranded (ss)DNA gate, the detailed mechanism is not fully understood. Here, we probe the catalytic steps of TRR using optical tweezers and fluorescence microscopy. We demonstrate that TRR forms an open gate in ssDNA of 8.5 ± 3.8 nm, and directly visualize binding of a second ssDNA or double-stranded (ds)DNA molecule to the open TRR-ssDNA gate, followed by catenation in each case. Strikingly, dsDNA binding increases the gate size (by ~16%), while BLM alters the mechanical flexibility of the gate. These findings reveal an unexpected plasticity of the TRR-ssDNA gate size and suggest that TRR-mediated transfer of dsDNA may be more relevant in vivo than previously believed.
Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis
Authors: Lee Chanbin , Kim Jieun , Han Jinsol , Oh Dayoung , Kim Minju , Jeong Hayeong , Kim Tae-Jin , Kim Sang-Woo , Kim Jeong Nam , Seo Young-Su , Suzuki Ayako , Kim Jae Ho , Jung Youngmi 
Published: January 2022

AbstractNonalcoholic fatty liver disease (NAFLD) is an important health concern worldwide and progresses into nonalcoholic steatohepatitis (NASH). Although prevalence and severity of NAFLD/NASH are higher in men than premenopausal women, it remains unclear how sex affects NAFLD/NASH pathophysiology. Formyl peptide receptor 2 (FPR2) modulates inflammatory responses in several organs; however, its role in the liver is unknown. Here we show that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH. NASH-like liver injury was induced in both sexes during choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) feeding, but compared with females, male mice had more severe hepatic damage. Fpr2 was more highly expressed in hepatocytes and healthy livers from females than males, and FPR2 deletion exacerbated liver damage in CDAHFD-fed female mice. Estradiol induced Fpr2 expression, which protected hepatocytes and the liver from damage. In conclusion, our results demonstrate that FPR2 mediates sex-specific responses to diet-induced NAFLD/NASH, suggesting a novel therapeutic target for NAFLD/NASH.
NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model
Authors: Qi Guangjian , Zhang Pei , Li Tongxia , Li Ming , Zhang Qian , He Feng , Zhang Lijun , Cai Hongwei , Lv Xinyuan , Qiao Haifa , Chen Xiaoqian , Ming Jie , Tian Bo 
Published: January 2022

AbstractEmotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.
Oscillating the local milieu of polymersome interiors via single input-regulated bilayer crosslinking and permeability tuning
Authors: Liu Guhuan , Tan Jiajia , Cen Jie , Zhang Guoying , Hu Jinming , Liu Shiyong 
Published: January 2022

AbstractThe unique permselectivity of cellular membranes is of crucial importance to maintain intracellular homeostasis while adapting to microenvironmental changes. Although liposomes and polymersomes have been widely engineered to mimic microstructures and functions of cells, it still remains a considerable challenge to synergize the stability and permeability of artificial cells and to imitate local milieu fluctuations. Herein, we report concurrent crosslinking and permeabilizing of pH-responsive polymersomes containing Schiff base moieties within bilayer membranes via enzyme-catalyzed acid production. Notably, this synergistic crosslinking and permeabilizing strategy allows tuning of the mesh sizes of the crosslinked bilayers with subnanometer precision, showing discriminative permeability toward maltooligosaccharides with molecular sizes of ~1.4-2.6 nm. The permselectivity of bilayer membranes enables intravesicular pH oscillation, fueled by a single input of glucose. This intravesicular pH oscillation can further drive the dissipative self-assembly of pH-sensitive dipeptides. Moreover, the permeabilization of polymersomes can be regulated by intracellular pH gradient as well, enabling the controlled release of encapsulated payloads.
Episodic back-arc spreading centre jumps controlled by transform fault to overriding plate strength ratio
Authors: Schliffke Nicholas , van Hunen Jeroen , Allen Mark B. , Magni Valentina , Gueydan Frédéric 
Published: January 2022

AbstractSpreading centre jumps are a common feature of oceanic back-arc basins. Jumps are conventionally suggested to be triggered by plate velocity changes, pre-existing weaknesses, or punctuated events such as the opening of slab windows. Here, we present 3D numerical models of back-arc spreading centre jumps evolving naturally in a homogeneous subduction system surrounded by continents without a trigger event. Spreading centres jump towards their subduction zone if the distance from trench to spreading centre becomes too long. In particular, jumps to a new spreading centre occur when the resistance on the boundary transform faults enabling relative motion of back-arc and neighbouring plates is larger than the resistance to break the overriding plate closer to trench. Time and distance of spreading centres jumps are, thus, controlled by the ratio between the transform fault and overriding plate strengths. Despite being less complex than natural systems, our models explain why narrow subducting plates (e.g. Calabrian slab), have more frequent and closely-spaced spreading jumps than wider subduction zones (e.g. Scotia). It also explains why wide back-arc basins undergo no spreading centre jumps in their life cycle.
CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells
Authors: Hebbar Nikhil , Epperly Rebecca , Vaidya Abishek , Thanekar Unmesha , Moore Sarah E. , Umeda Masayuki , Ma Jing , Patil Sagar L. , Langfitt Deanna , Huang Sujuan , Cheng Cheng , Klco Jeffery M. , Gottschalk Stephen , Velasquez M. Paulina 
Published: January 2022

AbstractDeveloping CAR T cells for acute myeloid leukemia (AML) has been hampered by a paucity of targets that are expressed on AML blasts and not on hematopoietic progenitor cells (HPCs). Here we demonstrate that GRP78 is expressed on the cell surface of primary AML blasts but not HPCs. To target GRP78, we generate T cell expressing a GRP78-specific peptide-based CAR, which show evidence of minimal fratricide post activation/transduction and antigen-dependent T cell differentiation. GRP78-CAR T cells recognize and kill GRP78-positive AML cells without toxicity to HPCs. In vivo, GRP78-CAR T cells have significant anti-AML activity. To prevent antigen-dependent T cell differentiation, we block CAR signaling and GRP78 cell surface expression post activation by using dasatinib during GRP78-CAR T cell manufacturing. This significantly improves their effector function in vitro and in vivo. Thus, targeting cell surface GRP78-positive AML with CAR T cells is feasible, and warrants further active exploration.
Splicing is an alternate oncogenic pathway activation mechanism in glioma
Authors: Siddaway Robert , Milos Scott , Vadivel Arun Kumaran Anguraj , Dobson Tara H. W. , Swaminathan Jyothishmathi , Ryall Scott , Pajovic Sanja , Patel Palak G. , Nazarian Javad , Becher Oren , Brudno Michael , Ramani Arun , Gopalakrishnan Vidya , Hawkins Cynthia 
Published: January 2022

AbstractHigh-grade diffuse glioma (HGG) is the leading cause of brain tumour death. While the genetic drivers of HGG have been well described, targeting these has thus far had little impact on survival suggesting other mechanisms are at play. Here we interrogate the alternative splicing landscape of pediatric and adult HGG through multi-omic analyses, uncovering an increased splicing burden compared with normal brain. The rate of recurrent alternative splicing in cancer drivers exceeds their mutation rate, a pattern that is recapitulated in pan-cancer analyses, and is associated with worse prognosis in HGG. We investigate potential oncogenicity by interrogating cancer pathways affected by alternative splicing in HGG; spliced cancer drivers include members of the RAS/MAPK pathway. RAS suppressor neurofibromin 1 is differentially spliced to a less active isoform in >80% of HGG downstream from REST upregulation, activating the RAS/MAPK pathway and reducing glioblastoma patient survival. Overall, our results identify non-mutagenic mechanisms by which cancers activate oncogenic pathways which need to accounted for in personalized medicine approaches.
Geminiviruses employ host DNA glycosylases to subvert DNA methylation-mediated defense
Authors: Gui Xiaojian , Liu Chang , Qi Yijun , Zhou Xueping 
Published: January 2022

AbstractDNA methylation is an epigenetic mechanism that plays important roles in gene regulation and transposon silencing. Active DNA demethylation has evolved to counterbalance DNA methylation at many endogenous loci. Here, we report that active DNA demethylation also targets viral DNAs, tomato yellow leaf curl China virus (TYLCCNV) and its satellite tomato yellow leaf curl China betasatellite (TYLCCNB), to promote their virulence. We demonstrate that the βC1 protein, encoded by TYLCCNB, interacts with a ROS1-like DNA glycosylase in Nicotiana benthamiana and with the DEMETER (DME) DNA glycosylase in Arabidopsis thaliana. The interaction between βC1 and DME facilitates the DNA glycosylase activity to decrease viral DNA methylation and promote viral virulence. These findings reveal that active DNA demethylation can be regulated by a viral protein to subvert DNA methylation-mediated defense.
Removal of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica
Authors: Ma Yongshuo , Liu Nian , Greisen Per , Li Jingbo , Qiao Kangjian , Huang Sanwen , Stephanopoulos Gregory 
Published: January 2022

AbstractSubstrate inhibition of enzymes can be a major obstacle to the production of valuable chemicals in engineered microorganisms. Here, we show substrate inhibition of lycopene cyclase as the main limitation in carotenoid biosynthesis in Yarrowia lipolytica. To overcome this bottleneck, we exploit two independent approaches. Structure-guided protein engineering yields a variant, Y27R, characterized by complete loss of substrate inhibition without reduction of enzymatic activity. Alternatively, establishing a geranylgeranyl pyrophosphate synthase-mediated flux flow restrictor also prevents the onset of substrate inhibition by diverting metabolic flux away from the inhibitory metabolite while maintaining sufficient flux towards product formation. Both approaches result in high levels of near-exclusive β-carotene production. Ultimately, we construct strains capable of producing 39.5 g/L β-carotene at a productivity of 0.165 g/L/h in bioreactor fermentations (a 1441-fold improvement over the initial strain). Our findings provide effective approaches for removing substrate inhibition in engineering pathways for efficient synthesis of natural products.
T cell responses to SARS-CoV-2 spike cross-recognize Omicron
Authors: Keeton Roanne , Tincho Marius B. , Ngomti Amkele , Baguma Richard , Benede Ntombi , Suzuki Akiko , Khan Khadija , Cele Sandile , Bernstein Mallory , Karim Farina , Madzorera Sharon V. , Moyo-Gwete Thandeka , Mennen Mathilda , Skelem Sango , Adriaanse Marguerite , Mutithu Daniel , Aremu Olukayode , Stek Cari , du Bruyn Elsa , Van Der Mescht Mieke A. , de Beer Zelda , de Villiers Talita R. , Bodenstein Annie , van den Berg Gretha , Mendes Adriano , Strydom Amy , Venter Marietjie , Giandhari Jennifer , Naidoo Yeshnee , Pillay Sureshnee , Tegally Houriiyah , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Wilkinson Robert J. , de Oliveira Tulio , Bekker Linda-Gail , Gray Glenda , Ueckermann Veronica , Rossouw Theresa , Boswell Michael T. , Bhiman Jinal N. , Moore Penny L. , Sigal Alex , Ntusi Ntobeko A. B. , Burgers Wendy A. , Riou Catherine 
Published: January 2022

AbstractThe SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9–12.
A knowledge graph to interpret clinical proteomics data
Authors: Santos Alberto , Colaço Ana R. , Nielsen Annelaura B. , Niu Lili , Strauss Maximilian , Geyer Philipp E. , Coscia Fabian , Albrechtsen Nicolai J. Wewer , Mundt Filip , Jensen Lars Juhl , Mann Matthias 
Published: January 2022

AbstractImplementing precision medicine hinges on the integration of omics data, such as proteomics, into the clinical decision-making process, but the quantity and diversity of biomedical data, and the spread of clinically relevant knowledge across multiple biomedical databases and publications, pose a challenge to data integration. Here we present the Clinical Knowledge Graph (CKG), an open-source platform currently comprising close to 20 million nodes and 220 million relationships that represent relevant experimental data, public databases and literature. The graph structure provides a flexible data model that is easily extendable to new nodes and relationships as new databases become available. The CKG incorporates statistical and machine learning algorithms that accelerate the analysis and interpretation of typical proteomics workflows. Using a set of proof-of-concept biomarker studies, we show how the CKG might augment and enrich proteomics data and help inform clinical decision-making.