bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Note on the Neo-Fisher Effect in the New Keynesian Model
Authors: Ali Syed Zahid , Qureshi Irfan A. 
Published: November 2022

AbstractTypically, contractionary monetary policy shocks increase the nominal and real rate of interest, which reduces both inflation and output . In contrast, the neo-Fisher effect (NFE) suggests that a transitory but persistent increase in the nominal rate of interest increases inflation in the short run. In a New Keynesian model augmented with several frictions, including the cost channel of monetary policy, real wage rigidity, habit formation in consumption, dampened expectations, and anticipated monetary policy shocks, we derive analytical conditions that give rise to (or avert) the NFE. We show that the NFE can arise due to the interplay between these frictions, and not only when the persistence of the policy shock is large, or when agents are forward-looking, as documented by the existing literature.
Multiple herbicide resistance in waterhemp (Amaranthus tuberculatus) accessions from Wisconsin
Authors: Faleco Felipe A. , Oliveira Maxwel C. , Arneson Nicholas J. , Renz Mark , Stoltenberg David E. , Werle Rodrigo 
Published: November 2022

AbstractA comprehensive, Wisconsin state-wide assessment of waterhemp response to a diverse group of herbicide sites of action has not been conducted. Our objective was to characterize the response of a state-wide collection of waterhemp accessions to postemergence (POST) and preemergence (PRE) herbicides commonly used in corn and soybean in Wisconsin. Greenhouse experiments were conducted with more than 80 accessions from 27 counties. POST treatments included 2,4-D, atrazine, dicamba, fomesafen, glufosinate, glyphosate, imazethapyr, and mesotrione at 1× and 3× label rates. PRE treatments included atrazine, fomesafen, mesotrione, metribuzin, and S-metolachlor at 0.5×, 1×, and 3× label rates. Ninety-eight percent and 88% of the accessions exhibited ≥50% plant survival after exposure to imazethapyr and glyphosate POST 3× rate, respectively. Seventeen percent, 16%, and 3% of the accessions exhibited ≥50% plant survival after exposure to 2,4-D, atrazine, and dicamba, respectively, applied POST at the 1× rate. Survival of all accessions was ≤25% after exposure to 2,4-D or dicamba applied POST at the 3× rate, or glufosinate, fomesafen, and mesotrione applied POST at either rate evaluated. No plant of any accession survived exposure to glufosinate at either rate. Forty-five percent and 3% of the accessions exhibited <90% plant density reduction after exposure to atrazine applied PRE at the 3× rate and fomesafen PRE at the 1× rate, respectively. Plant density reduction of all accessions was ≥96% after exposure to fomesafen applied PRE at the 3× rate, or metribuzin, S-metolachlor, and mesotrione applied PRE at the 1× rate. Our results suggest that waterhemp resistance to imazethapyr and glyphosate applied POST is widespread in Wisconsin, whereas resistance to 2,4-D, atrazine, and dicamba applied POST is present to a lower extent. One accession (A75, Fond du Lac County) exhibited multiple resistance to imazethapyr, atrazine, glyphosate, and 2,4-D when applied POST. Overall, atrazine applied PRE was ineffective for waterhemp control in Wisconsin. Proactive resistance management and the use of effective PRE and POST herbicides are fundamental for waterhemp management in Wisconsin.
Assessment and Constraint of Mesozooplankton in CMIP6 Earth System Models
Authors: Petrik C. M. , Luo J. Y. , Heneghan R. F. , Everett J. D. , Harrison C. S. , Richardson A. J. 
Published: November 2022

AbstractAlthough zooplankton play a substantial role in the biological carbon pump and serve as a crucial link between primary producers and higher trophic level consumers, the skillful representation of zooplankton is not often a focus of ocean biogeochemical models. Systematic evaluations of zooplankton in models could improve their representation, but so far, ocean biogeochemical skill assessment of Earth system model (ESM) ensembles have not included zooplankton. Here we use a recently developed global, observationally based map of mesozooplankton biomass to assess the skill of mesozooplankton in six CMIP6 ESMs. We also employ a biome‐based assessment of the ability of these models to reproduce the observed relationship between mesozooplankton biomass and surface chlorophyll. The combined analysis found that most models were able to reasonably simulate the large regional variations in mesozooplankton biomass at the global scale. Additionally, three of the ESMs simulated a mesozooplankton‐chlorophyll relationship within the observational bounds, which we used as an emergent constraint on future mesozooplankton projections. We highlight where differences in model structure and parameters may give rise to varied mesozooplankton distributions under historic and future conditions, and the resultant wide ensemble spread in projected changes in mesozooplankton biomass. Despite differences, the strength of the mesozooplankton‐chlorophyll relationships across all models was related to the projected changes in mesozooplankton biomass globally and in regional biomes. These results suggest that improved observations of mesozooplankton and their relationship to chlorophyll will better constrain projections of climate change impacts on these important animals.
Evidence for Turbulent Magnetic Diffusion in Earth's Core
Authors: Holdenried‐Chernoff D. , Buffett B. A. 
Published: November 2022

AbstractFluctuations in the paleomagnetic field suggest that the dipole decay time is shorter than expected, based on current estimates for the molecular magnetic diffusivity in the outer core. Similar behavior is observed in turbulent dynamo simulations, where the short magnetic field decay time cannot be attributed to higher‐order decay modes. We interpret the short decay time as a signature of turbulent diffusion and show that mean‐field theory can quantitatively account for the dynamo results. The predictions depend on the amplitude and length scale of the flow that interacts with the magnetic field. We rely on the pairwise balance between Lorentz/Coriolis and buoyancy/Coriolis forces to identify the relevant part of the flow, and use the resulting flow properties to reproduce results from numerical dynamo simulations within their uncertainties. Upon extending these predictions to the paleomagnetic field, we find that the inferred decay time requires a bulk root‐mean‐square velocity less than 0.8–1.2 mm s−1. Somewhat lower velocities have been estimated at the top of the core from observations of secular variation. These results show that velocities in the interior of the core are constrained by paleomagnetic observations, and that the amplitude of this flow cannot substantially exceed estimates at the core surface.
The 2020 Westmorland, California Earthquake Swarm as Aftershocks of a Slow Slip Event Sustained by Fluid Flow
Authors: Sirorattanakul Krittanon , Ross Zachary E. , Khoshmanesh Mostafa , Cochran Elizabeth S. , Acosta Mateo , Avouac Jean‐Philippe 
Published: November 2022

AbstractSwarms are bursts of earthquakes without an obvious mainshock. Some have been observed to be associated with transient aseismic fault slip, while others are thought to be related to fluids. However, the association is rarely quantitative due to insufficient data quality. We use high‐quality GPS/GNSS, InSAR, and relocated seismicity to study a swarm of >2,000 earthquakes which occurred between 30 September and 6 October 2020, near Westmorland, California. Using 5 min sampled Global Positioning System (GPS) supplemented with InSAR, we document a spontaneous shallow Mw 5.2 slow slip event that preceded the swarm by 2–15 hr. The earthquakes in the early phase were predominantly non‐interacting and driven primarily by the slow slip event resulting in a nonlinear expansion. A stress‐driven model based on the rate‐and‐state friction successfully explains the overall spatial and temporal evolution of earthquakes, including the time lag between the onset of the slow slip event and the swarm. Later, a distinct back front and a square root of time expansion of clustered seismicity on en‐echelon fault structures suggest that fluids helped sustain the swarm. Static stress triggering analysis using Coulomb stress and statistics of interevent times suggest that 45%–65% of seismicity was driven by the slow slip event, 10%–35% by inter‐earthquake interactions, and 10%–30% by fluids. Our model also provides constraints on the friction parameter and the pore pressure and suggests that this swarm behaved like an aftershock sequence but with the mainshock replaced by the slow slip event.
Temperature Variability and Eddy‐Flow Interaction in the South of Oyashio Extension
Authors: Yang Haiyuan , Zhu Ruichen , Chen Zhaohui , Li Jianchao , Wu Lixin 
Published: November 2022

AbstractBased on observations and eddy‐resolving model products, this study investigates the temperature variability south of the Oyashio Extension (OE). During 2016–2021, six dramatic cold events, which significantly impact the local ecosystems, are captured by in situ and satellite observations. It reveals that interaction between the OE front (OEF) and anticyclonic mesoscale eddies originating from the Kuroshio Extension is responsible for these cold events. Accompanied by intense eddy‐flow baroclinic energy exchange, the OEF meanders to the south and favors a southward cold‐water intrusion. Further analysis illustrates that the cold events tend to occur during spring and autumn, which is associated with the seasonal evolutions of OEF and anticyclonic eddies.
WNK3 inhibition elicits antitumor immunity by suppressing PD-L1 expression on tumor cells and activating T-cell function
Authors: Yoon Hyun Ju , Kim Gi-Cheon , Oh Sejin , Kim Hakhyun , Kim Yong Keon , Lee Yunji , Kim Min Seo , Kwon Gino , Ok Yeon-Su , Kwon Ho-Keun , Kim Hyun Seok 
Published: November 2022

AbstractImmune checkpoint therapies, such as programmed cell death ligand 1 (PD-L1) blockade, have shown remarkable clinical benefit in many cancers by restoring the function of exhausted T cells. Hence, the identification of novel PD-L1 regulators and the development of their inhibition strategies have significant therapeutic advantages. Here, we conducted pooled shRNA screening to identify regulators of membrane PD-L1 levels in lung cancer cells targeting druggable genes and cancer drivers. We identified WNK lysine deficient protein kinase 3 (WNK3) as a novel positive regulator of PD-L1 expression. The kinase-dead WNK3 mutant failed to elevate PD-L1 levels, indicating the involvement of its kinase domain in this function. WNK3 perturbation increased cancer cell death in cancer cell–immune cell coculture conditions and boosted the secretion of cytokines and cytolytic enzymes, promoting antitumor activities in CD4+ and CD8+ T cells. WNK463, a pan-WNK inhibitor, enhanced CD8+ T-cell-mediated antitumor activity and suppressed tumor growth as a monotherapy as well as in combination with a low-dose anti-PD-1 antibody in the MC38 syngeneic mouse model. Furthermore, we demonstrated that the c-JUN N-terminal kinase (JNK)/c-JUN pathway underlies WNK3-mediated transcriptional regulation of PD-L1. Our findings highlight that WNK3 inhibition might serve as a potential therapeutic strategy for cancer immunotherapy through its concurrent impact on cancer cells and immune cells.
The natural product salicin alleviates osteoarthritis progression by binding to IRE1α and inhibiting endoplasmic reticulum stress through the IRE1α-IκBα-p65 signaling pathway
Authors: Zhu Zhenglin , Gao Shengqiang , Chen Cheng , Xu Wei , Xiao Pengcheng , Chen Zhiyu , Du Chengcheng , Chen Bowen , Gao Yan , Wang Chunli , Liao Junyi , Huang Wei 
Published: November 2022

AbstractDespite the high prevalence of osteoarthritis (OA) in older populations, disease-modifying OA drugs (DMOADs) are still lacking. This study was performed to investigate the effects and mechanisms of the small molecular drug salicin (SA) on OA progression. Primary rat chondrocytes were stimulated with TNF-α and treated with or without SA. Inflammatory factors, cartilage matrix degeneration markers, and cell proliferation and apoptosis markers were detected at the mRNA and protein levels. Cell proliferation and apoptosis were evaluated by EdU assays or flow cytometric analysis. RNA sequencing, molecular docking and drug affinity-responsive target stability analyses were used to clarify the mechanisms. The rat OA model was used to evaluate the effect of intra-articular injection of SA on OA progression. We found that SA rescued TNF-α-induced degeneration of the cartilage matrix, inhibition of chondrocyte proliferation, and promotion of chondrocyte apoptosis. Mechanistically, SA directly binds to IRE1α and occupies the IRE1α phosphorylation site, preventing IRE1α phosphorylation and regulating IRE1α-mediated endoplasmic reticulum (ER) stress by IRE1α-IκBα-p65 signaling. Finally, intra-articular injection of SA-loaded lactic-co-glycolic acid (PLGA) ameliorated OA progression by inhibiting IRE1α-mediated ER stress in the OA model. In conclusion, SA alleviates OA by directly binding to the ER stress regulator IRE1α and inhibits IRE1α-mediated ER stress via IRE1α-IκBα-p65 signaling. Topical use of the small molecular drug SA shows potential to modify OA progression.
Plant-associated Bacillus mobilizes its secondary metabolites upon perception of the siderophore pyochelin produced by a Pseudomonas competitor
Authors: Andrić Sofija , Rigolet Augustin , Argüelles Arias Anthony , Steels Sébastien , Hoff Grégory , Balleux Guillaume , Ongena Loïc , Höfte Monica , Meyer Thibault , Ongena Marc 
Published: November 2022

Abstract
Bacillus velezensis is considered as model species for plant-associated bacilli providing benefits to its host such as protection against phytopathogens. This is mainly due to the potential to secrete a wide range of secondary metabolites with specific and complementary bioactivities. This metabolite arsenal has been quite well defined genetically and chemically but much remains to be explored regarding how it is expressed under natural conditions and notably how it can be modulated upon interspecies interactions in the competitive rhizosphere niche. Here, we show that B. velezensis can mobilize a substantial part of its metabolome upon the perception of Pseudomonas, as a soil-dwelling competitor. This metabolite response reflects a multimodal defensive strategy as it includes polyketides and the bacteriocin amylocyclicin, with broad antibiotic activity, as well as surfactin lipopeptides, contributing to biofilm formation and enhanced motility. Furthermore, we identified the secondary Pseudomonas siderophore pyochelin as an info-chemical, which triggers this response via a mechanism independent of iron stress. We hypothesize that B. velezensis relies on such chelator sensing to accurately identify competitors, illustrating a new facet of siderophore-mediated interactions beyond the concept of competition for iron and siderophore piracy. This phenomenon may thus represent a new component of the microbial conversations driving the behavior of members of the rhizosphere community.
Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC
Authors: Wang Longhao , Hu Tao , Shen Zhibo , Zheng Yuanyuan , Geng Qishun , Li Lifeng , Sha Beibei , Li Miaomiao , Sun Yaxin , Guo Yongjun , Xue Wenhua , Xuan Dan , Chen Ping , Zhao Jie 
Published: November 2022

AbstractThe deubiquitinating enzyme USP1 (ubiquitin-specific protease 1) plays a role in the progression of various tumors, emerging as a potential therapeutic target. This study aimed to determine the role of USP1 as a therapeutic target in hepatocellular carcinoma (HCC). We detected USP1 expression in the tumor and adjacent tissues of patients with HCC using immunohistochemical staining. We evaluated the effect of the USP1 inhibitor ML-323 on HCC cell proliferation and cell cycle using a CCK-8 cell-counting kit and plate cloning assays, and propidium iodide, respectively. Apoptosis was detected by annexin V-FITC/Propidium Iodide (PI) staining and caspase 3 (casp3) activity. Transmission electron microscopy and LC3B immunofluorescence were used to detect autophagy. Western blotting was used to detect the accumulation of ubiquitinated proteins, the expression of endoplasmic reticulum (ER) stress-related proteins, and the AMPK-ULK1/ATG13 signaling pathway. We demonstrated that ML-323 inhibits the growth of HCC cells and induces G1 phase cell cycle arrest by regulating cyclin expression. ML-323 treatment resulted in the accumulation of ubiquitinated proteins, induced ER stress, and triggered Noxa-dependent apoptosis, which was regulated by the Activating Transcription Factor 4(ATF4). Moreover, active ER stress induces protective autophagy by increasing AMPK phosphorylation; therefore, we inhibited ER stress using 4-Phenylbutyric acid (4-PBA), which resulted in ER stress reduction, apoptosis, and autophagy in ML-323-treated HCC cells. In addition, blocking autophagy using the AMPK inhibitor compound C (CC), chloroquine (CQ), or bafilomycin A1 (BafA1) enhanced the cytotoxic effect of ML-323. Our findings revealed that targeting USP1 may be a potential strategy for the treatment of HCC.
SR9009 inhibits lethal prostate cancer subtype 1 by regulating the LXRα/FOXM1 pathway independently of REV-ERBs
Authors: Xu Hang , Zhang Jiapeng , Zheng Xiaonan , Tan Ping , Xiong Xingyu , Yi Xianyanling , Yang Yang , Wang Yan , Liao Dazhou , Li Hong , Wei Qiang , Ai Jianzhong , Yang Lu 
Published: November 2022

AbstractPerturbations of the circadian clock are linked to multiple diseases, including cancers. Pharmacological activation of REV-ERB nuclear receptors, the core components of the circadian clock, has antitumor effects on various malignancies, while the impact of SR9009 on prostate cancer (PCa) remains unknown. Here, we found that SR9009 was specifically lethal to PCa cell lines but had no cytotoxic effect on prostate cells. SR9009 significantly inhibited colony formation, the cell cycle, and cell migration and promoted apoptosis in PCa cells. SR9009 treatment markedly inhibited prostate cancer subtype 1 (PCS1), the most lethal and aggressive PCa subtype, through FOXM1 pathway blockade, while it had no impacts on PCS2 and PCS3. Seven representative genes, including FOXM1, CENPA, CENPF, CDK1, CCNB1, CCNB2, and BIRC5, were identified as the shared genes involved in the FOXM1 pathway and PCS1. All of these genes were upregulated in PCa tissues, associated with worse clinicopathological outcomes and downregulated after SR9009 treatment. Nevertheless, knockdown or knockout of REV-ERB could not rescue the anticancer effect of SR9009 in PCa. Further analysis confirmed that it was LXRα rather than REV-ERBs which has been activated by SR9009. The expression levels of these seven genes were changed correspondingly after LXRα knockdown and SR9009 treatment. An in vivo study validated that SR9009 restrained tumor growth in 22RV1 xenograft models and inhibited FOXM1 and its targeted gene expression. In summary, SR9009 can serve as an effective treatment option for highly aggressive and lethal PCS1 tumors through mediating the LXRα/FOXM1 pathway independently of REV-ERBs.
MYBPC3 deficiency in cardiac fibroblasts drives their activation and contributes to fibrosis
Authors: Zou Xiaodong , Ouyang Hongsheng , Lin Feng , Zhang Huanyu , Yang Yang , Pang Daxin , Han Renzhi , Tang Xiaochun 
Published: November 2022

AbstractGenetic mutations in the MYBPC3 gene encoding cardiac myosin binding protein C (cMyBP-C) are the most common cause of hypertrophic cardiomyopathy (HCM). Myocardial fibrosis (MF) plays a critical role in the development of HCM. However, the mechanism for mutant MYBPC3-induced MF is not well defined. In this study, we developed a R495Q mutant pig model using cytosine base editing and observed an early-onset MF in these mutant pigs shortly after birth. Unexpectedly, we found that the “cardiac-specific” MYBPC3 gene was actually expressed in cardiac fibroblasts from different species as well as NIH3T3 fibroblasts at the transcription and protein levels. CRISPR-mediated disruption of Mybpc3 in NIH3T3 fibroblasts activated nuclear factor κB (NF-κB) signaling pathway, which increased the expression of transforming growth factor beta (TGF-β1) and other pro-inflammatory genes. The upregulation of TGF-β1 promoted the expression of hypoxia-inducible factor-1 subunit α (HIF-1α) and its downstream targets involved in glycolysis such as GLUT1, PFK, and LDHA. Consequently, the enhanced aerobic glycolysis with higher rate of ATP biosynthesis accelerated the activation of cardiac fibroblasts, contributing to the development of HCM. This work reveals an intrinsic role of MYBPC3 in maintaining cardiac fibroblast homeostasis and disruption of MYBPC3 in these cells contributes to the disease pathogenesis of HCM.
Is there a “pandemic effect” on individuals’ willingness to take genetic tests?
Authors: Deruelle Thibaud , Kalouguina Veronika , Trein Philipp , Wagner Joël 
Published: November 2022

AbstractIn this cross-sectional, semi-longitudinal and quasi-experimental study, our goal was to determine the effect of data storage conditions on willingness to take a genetic test. We compared individuals’ preferences regarding how they want to store health data collected from genetic tests through two survey experiments fielded in Switzerland in March 2020 and January 2022. We tested for differences whether genetic data are presented as private goods or public goods. Results confirm our initial research expectation: more control over storage increases willingness, so does framing genetic data as private good. However, they also show that the willingness to take a genetic test has noticeably increased between 2020 and 2022. Our results point toward a “pandemic effect” which would have increased willingness take a genetic test, nevertheless, more data are needed to understand this putative effect.
Magic-angle-spinning NMR structure of the kinesin-1 motor domain assembled with microtubules reveals the elusive neck linker orientation
Authors: Zhang Chunting , Guo Changmiao , Russell Ryan W. , Quinn Caitlin M. , Li Mingyue , Williams John C. , Gronenborn Angela M. , Polenova Tatyana 
Published: November 2022

AbstractMicrotubules (MTs) and their associated proteins play essential roles in maintaining cell structure, organelle transport, cell motility, and cell division. Two motors, kinesin and cytoplasmic dynein link the MT network to transported cargos using ATP for force generation. Here, we report an all-atom NMR structure of nucleotide-free kinesin-1 motor domain (apo-KIF5B) in complex with paclitaxel-stabilized microtubules using magic-angle-spinning (MAS) NMR spectroscopy. The structure reveals the position and orientation of the functionally important neck linker and how ADP induces structural and dynamic changes that ensue in the neck linker. These results demonstrate that the neck linker is in the undocked conformation and oriented in the direction opposite to the KIF5B movement. Chemical shift perturbations and intensity changes indicate that a significant portion of ADP-KIF5B is in the neck linker docked state. This study also highlights the unique capability of MAS NMR to provide atomic-level information on dynamic regions of biological assemblies.