bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Atmospheric Drivers in a Sudden Transition of California Precipitation in the 2012/13 Winter
Authors: Lim Yuna , Peings Yannick , Magnusdottir Gudrun 
Published: November 2021

AbstractCalifornia experienced a sharp transition from wet to historically dry conditions during the 2012/13 winter. Such transitions in the precipitation regime have strong consequences for water management, but predicting them at the seasonal time scale remains very challenging as little is known about what drives them. The 2012/13 winter was characterized by a neutral El Niño Southern Oscillation, strong Madden‐Julian Oscillation (MJO) activity, and sudden stratospheric warming. This study examines the potential influence of these different drivers in atmospheric global climate model experiments with prescribed sea surface temperature (SST) and sea ice concentration and constrained tropical and/or Arctic variability. Our model results are compared to reforecasts from the North American Multi‐Model Ensemble (NMME) and Subseasonal Experiment (SubX)/Subseasonal to Seasonal (S2S) projects to determine which important processes may have been missed by the seasonal prediction systems. Our simulations suggest that the tropical warm‐west, cool‐east SST anomaly played an active role in the wet conditions of November–December 2012 through a typical tropical‐extratropical teleconnection. The tropical SST anomalies were not accurately predicted by the NMME models, and none of them predicted the wet anomalies in November–December. In contrast, the sudden transition toward dry conditions in January is found to be independent of tropical SST variability, and rather influenced by strong MJO activity over the western Pacific. The SubX/S2S models with a better MJO prediction tend to predict the dry conditions in January better. Our study highlights how intraseasonal processes superimpose on more persistent seasonal anomalies and induce regime shifts such as the wet‐to‐dry transition of the 2012/13 winter.
Restoration of HBV-specific CD8+ T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-α therapy
Authors: Wang Dongyao , Fu Binqing , Shen Xiaokun , Guo Chuang , Liu Yanyan , Zhang Junfei , Sun Rui , Ye Ying , Li Jiabin , Tian Zhigang , Wei Haiming 
Published: November 2021

AbstractPatients with chronic hepatitis B (CHB) undergoing interferon (IFN)-α-based therapies often exhibit a poor HBeAg serological response. Thus, there is an unmet need for new therapies aimed at CHB. This study comprised two clinical trials, including 130 CHB patients, who were treatment-naïve; in the first, 92 patients were systematically analyzed ex vivo for interleukin-2 receptor (IL-2R) expression and inhibitory molecules expression after receiving Peg-IFN-α-2b therapy. In our second clinical trial, 38 non-responder patients, in whom IFN-α therapy had failed, were treated with or without low-dose IL-2 for 24 weeks. We then examined the hepatitis B virus (HBV)-specific CD8+T-cell response and the clinical outcome, in these patients. Although the majority of the participants undergoing Peg-IFN-α-2b therapy were non-responders, we observed a decrease in CD25 expression on their CD4+T cells, suggesting that IFN-α therapy may provide a rationale for sequential IL-2 treatment without increasing regulatory T cells (Tregs). Following sequential therapy with IL-2, we demonstrated that the non-responders experienced a decrease in the numbers of Tregs and programmed cell death protein 1 (PD-1) expression. In addition, sequential IL-2 administration rescued effective immune function, involving signal transducer and activator of transcription 1 (STAT1) activation. Importantly, IL-2 therapy significantly increased the frequency and function of HBV-specific CD8+T cells, which translated into improved clinical outcomes, including HBeAg seroconversion, among the non-responder CHB patients. Our findings suggest that sequential IL-2 therapy shows efficacy in rescuing immune function in non-responder patients with refractory CHB.
Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia
Authors: Costi Sara , Morris Laurel S. , Collins Abigail , Fernandez Nicolas F. , Patel Manishkumar , Xie Hui , Kim-Schulze Seunghee , Stern Emily R. , Collins Katherine A. , Cathomas Flurin , Parides Michael K. , Whitton Alexis E. , Pizzagalli Diego A. , Russo Scott J. , Murrough James W. 
Published: November 2021

AbstractIncreased levels of peripheral cytokines have been previously associated with depression in preclinical and clinical research. Although the precise nature of peripheral immune dysfunction in depression remains unclear, evidence from animal studies points towards a dysregulated response of peripheral leukocytes as a risk factor for stress susceptibility. This study examined dynamic release of inflammatory blood factors from peripheral blood mononuclear cells (PBMC) in depressed patients and associations with neural and behavioral measures of reward processing. Thirty unmedicated patients meeting criteria for unipolar depressive disorder and 21 healthy control volunteers were enrolled. PBMCs were isolated from whole blood and stimulated ex vivo with lipopolysaccharide (LPS). Olink multiplex assay was used to analyze a large panel of inflammatory proteins. Participants completed functional magnetic resonance imaging with an incentive flanker task to probe neural responses to reward anticipation, as well as clinical measures of anhedonia and pleasure including the Temporal Experience of Pleasure Scale (TEPS) and the Snaith-Hamilton Pleasure Scale (SHAPS). LPS stimulation revealed larger increases in immune factors in depressed compared to healthy subjects using an aggregate immune score (t49 = 2.83, p = 0.007). Higher peripheral immune score was associated with reduced neural responses to reward anticipation within the ventral striatum (VS) (r = −0.39, p = 0.01), and with reduced anticipation of pleasure as measured with the TEPS anticipatory sub-score (r = −0.318, p = 0.023). Our study provides new evidence suggesting that dynamic hyper-reactivity of peripheral leukocytes in depressed patients is associated with blunted activation of the brain reward system and lower subjective anticipation of pleasure.
Practice patterns and outcomes of direct oral anticoagulant use in myeloproliferative neoplasm patients
Authors: How Joan , Story Charlotte , Ren Siyang , Neuberg Donna , Rosovsky Rachel P. , Hobbs Gabriela S. , Connors Jean M. 
Published: November 2021

AbstractMyeloproliferative neoplasms (MPNs) are characterized by an increased risk of thrombosis and bleeding. Vitamin K antagonists (VKAs) are the historic anticoagulant recommended for use in MPNs. Direct oral anticoagulants (DOACs) are being increasingly used in general and cancer populations. However, DOAC safety and efficacy in MPN patients remains unclear. We characterized real-world practice patterns of DOAC use in MPN patients and evaluated thrombosis and bleeding risk. We conducted a retrospective cohort study of 133 MPN patients prescribed DOACs for venous thromboembolism (VTE), atrial fibrillation, or arterial thromboembolism (ATE). Practice patterns including duration of anticoagulation, dosing, and concomitant use of antiplatelet/cytoreductive agents, were heterogeneous among MPN patients. The 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5–9.5%) and 12.3% (6.4–18.2%) respectively. In comparison, reported bleeding rates in MPN patients on DOAC and VKAs are 1–3%. On multivariable analysis, prior history of thrombosis, use of dabigatran or edoxaban, and younger age were significantly associated with a higher risk of recurrent thrombosis, while leukocytosis was associated with a higher risk of bleeding on DOAC. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population.
Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2
Authors: Duan Chenyang , Kuang Lei , Hong Chen , Xiang Xinming , Liu Jiancang , Li Qinghui , Peng Xiaoyong , Zhou Yuanqun , Wang Hongchen , Liu Liangming , Li Tao 
Published: November 2021

AbstractMitochondrial mass imbalance is one of the key causes of cardiovascular dysfunction after hypoxia. The activation of dynamin-related protein 1 (Drp1), as well as its mitochondrial translocation, play important roles in the changes of both mitochondrial morphology and mitochondrial functions after hypoxia. However, in addition to mediating mitochondrial fission, whether Drp1 has other regulatory roles in mitochondrial homeostasis after mitochondrial translocation is unknown. In this study, we performed a series of interaction and colocalization assays and found that, after mitochondrial translocation, Drp1 may promote the excessive opening of the mitochondrial permeability transition pore (mPTP) after hypoxia. Firstly, mitochondrial Drp1 maximumly recognizes mPTP channels by binding Bcl-2-associated X protein (BAX) and a phosphate carrier protein (PiC) in the mPTP. Then, leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) is recruited, whose kinase activity is inhibited by direct binding with mitochondrial Drp1 after hypoxia. Subsequently, the mPTP-related protein hexokinase 2 (HK2) is inactivated at Thr-473 and dissociates from the mitochondrial membrane, ultimately causing structural disruption and overopening of mPTP, which aggravates mitochondrial and cellular dysfunction after hypoxia. Thus, our study interprets the dual direct regulation of mitochondrial Drp1 on mitochondrial morphology and functions after hypoxia and proposes a new mitochondrial fission-independent mechanism for the role of Drp1 after its translocation in hypoxic injury.
HNF4A defines tissue-specific circadian rhythms by beaconing BMAL1::CLOCK chromatin binding and shaping the rhythmic chromatin landscape
Authors: Qu Meng , Qu Han , Jia Zhenyu , Kay Steve A. 
Published: November 2021

AbstractTranscription modulated by the circadian clock is diverse across cell types, underlying circadian control of peripheral metabolism and its observed perturbation in human diseases. We report that knockout of the lineage-specifying Hnf4a gene in mouse liver causes associated reductions in the genome-wide distribution of core clock component BMAL1 and accessible chromatin marks (H3K4me1 and H3K27ac). Ectopically expressing HNF4A remodels chromatin landscape and nucleates distinct tissue-specific BMAL1 chromatin binding events, predominantly in enhancer regions. Circadian rhythms are disturbed in Hnf4a knockout liver and HNF4A-MODY diabetic model cells. Additionally, the epigenetic state and accessibility of the liver genome dynamically change throughout the day, synchronized with chromatin occupancy of HNF4A and clustered expression of circadian outputs. Lastly, Bmal1 knockout attenuates HNF4A genome-wide binding in the liver, likely due to downregulated Hnf4a transcription. Our results may provide a general mechanism for establishing circadian rhythm heterogeneity during development and disease progression, governed by chromatin structure.
Marine phytoplankton functional types exhibit diverse responses to thermal change
Authors: Anderson S. I. , Barton A. D. , Clayton S. , Dutkiewicz S. , Rynearson T. A. 
Published: November 2021

AbstractMarine phytoplankton generate half of global primary production, making them essential to ecosystem functioning and biogeochemical cycling. Though phytoplankton are phylogenetically diverse, studies rarely designate unique thermal traits to different taxa, resulting in coarse representations of phytoplankton thermal responses. Here we assessed phytoplankton functional responses to temperature using empirically derived thermal growth rates from four principal contributors to marine productivity: diatoms, dinoflagellates, cyanobacteria, and coccolithophores. Using modeled sea surface temperatures for 1950–1970 and 2080–2100, we explored potential alterations to each group’s growth rates and geographical distribution under a future climate change scenario. Contrary to the commonly applied Eppley formulation, our data suggest phytoplankton functional types may be characterized by different temperature coefficients (Q10), growth maxima thermal dependencies, and thermal ranges which would drive dissimilar responses to each degree of temperature change. These differences, when applied in response to global simulations of future temperature, result in taxon-specific projections of growth and geographic distribution, with low-latitude coccolithophores facing considerable decreases and cyanobacteria substantial increases in growth rates. These results suggest that the singular effect of changing temperature may alter phytoplankton global community structure, owing to the significant variability in thermal response between phytoplankton functional types.
Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma
Authors: Mahlokozera Tatenda , Patel Bhuvic , Chen Hao , Desouza Patrick , Qu Xuan , Mao Diane D. , Hafez Daniel , Yang Wei , Taiwo Rukayat , Paturu Mounica , Salehi Afshin , Gujar Amit D. , Dunn Gavin P. , Mosammaparast Nima , Petti Allegra A. , Yano Hiroko , Kim Albert H. 
Published: November 2021

AbstractThe pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance.
Current-induced manipulation of exchange bias in IrMn/NiFe bilayer structures
Authors: Kang Jaimin , Ryu Jeongchun , Choi Jong-Guk , Lee Taekhyeon , Park Jaehyeon , Lee Soogil , Jang Hanhwi , Jung Yeon Sik , Kim Kab-Jin , Park Byong-Guk 
Published: November 2021

AbstractThe electrical control of antiferromagnetic moments is a key technological goal of antiferromagnet-based spintronics, which promises favourable device characteristics such as ultrafast operation and high-density integration as compared to conventional ferromagnet-based devices. To date, the manipulation of antiferromagnetic moments by electric current has been demonstrated in epitaxial antiferromagnets with broken inversion symmetry or antiferromagnets interfaced with a heavy metal, in which spin-orbit torque (SOT) drives the antiferromagnetic domain wall. Here, we report current-induced manipulation of the exchange bias in IrMn/NiFe bilayers without a heavy metal. We show that the direction of the exchange bias is gradually modulated up to ±22 degrees by an in-plane current, which is independent of the NiFe thickness. This suggests that spin currents arising in the IrMn layer exert SOTs on uncompensated antiferromagnetic moments at the interface which then rotate the antiferromagnetic moments. Furthermore, the memristive features are preserved in sub-micron devices, facilitating nanoscale multi-level antiferromagnetic spintronic devices.
Supramolecular fibrillation of peptide amphiphiles induces environmental responses in aqueous droplets
Authors: Booth Richard , Insua Ignacio , Ahmed Sahnawaz , Rioboo Alicia , Montenegro Javier 
Published: November 2021

AbstractOne-dimensional (1D) supramolecular polymers are commonly found in natural and synthetic systems to prompt functional responses that capitalise on hierarchical molecular ordering. Despite amphiphilic self-assembly being significantly studied in the context of aqueous encapsulation and autopoiesis, very little is currently known about the physico-chemical consequences and functional role of 1D supramolecular polymerisation confined in aqueous compartments. Here, we describe the different phenomena that resulted from the chemically triggered supramolecular fibrillation of synthetic peptide amphiphiles inside water microdroplets. The confined connection of suitable dormant precursors triggered a physically autocatalysed chemical reaction that resulted in functional environmental responses such as molecular uptake, fusion and chemical exchange. These results demonstrate the potential of minimalistic 1D supramolecular polymerisation to modulate the behaviour of individual aqueous entities with their environment and within communities.
Predicting thickness perception of liquid food products from their non-Newtonian rheology
Authors: Deblais Antoine , Hollander Elyn den , Boucon Claire , Blok Annelies E. , Veltkamp Bastiaan , Voudouris Panayiotis , Versluis Peter , Kim Hyun-Jung , Mellema Michel , Stieger Markus , Bonn Daniel , Velikov Krassimir P. 
Published: November 2021

AbstractThe “mouthfeel” of food products is a key factor in our perception of food quality and in our appreciation of food products. Extensive research has been performed on what determines mouthfeel, and how it can be linked to laboratory measurements and eventually predicted. This was mainly done on the basis of simple models that do not accurately take the rheology of the food products into account. Here, we show that the subjectively perceived “thickness” of liquid foods, or the force needed to make the sample flow or deform in the mouth, can be directly related to their non-Newtonian rheology. Measuring the shear-thinning rheology and modeling the squeeze flow between the tongue and the palate in the oral cavity allows to predict how a panel perceives soup “thickness”. This is done for various liquid bouillons with viscosities ranging from that of water to low-viscous soups and for high-viscous xanthan gum solutions. Our findings show that our tongues, just like our eyes and ears, are logarithmic measuring instruments in agreement with the Weber-Fechner law that predicts a logarithmic relation between stimulus amplitude and perceived strength. Our results pave the way for more accurate prediction of mouthfeel characteristics of liquid food products.
Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing
Authors: Chakraborty Sayan , Sampath Divyaleka , Yu Lin Melissa Ong , Bilton Matthew , Huang Cheng-Kuang , Nai Mui Hoon , Njah Kizito , Goy Pierre-Alexis , Wang Cheng-Chun , Guccione Ernesto , Lim Chwee-Teck , Hong Wanjin 
Published: November 2021

AbstractAn orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin’s mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche.
Arabidopsis P4 ATPase-mediated cell detoxification confers resistance to Fusarium graminearum and Verticillium dahliae
Authors: Wang Fanlong , Li Xianbi , Li Yujie , Han Jing , Chen Yang , Zeng Jianyan , Su Mei , Zhuo Jingxin , Ren Hui , Liu Haoru , Hou Lei , Fan Yanhua , Yan Xingying , Song Shuiqing , Zhao Juan , Jin Dan , Zhang Mi , Pei Yan 
Published: November 2021

AbstractMany toxic secondary metabolites produced by phytopathogens can subvert host immunity, and some of them are recognized as pathogenicity factors. Fusarium head blight and Verticillium wilt are destructive plant diseases worldwide. Using toxins produced by the causal fungi Fusarium graminearum and Verticillium dahliae as screening agents, here we show that the Arabidopsis P4 ATPases AtALA1 and AtALA7 are responsible for cellular detoxification of mycotoxins. Through AtALA1-/AtALA7-mediated vesicle transport, toxins are sequestered in vacuoles for degradation. Overexpression of AtALA1 and AtALA7 significantly increases the resistance of transgenic plants to F. graminearum and V. dahliae, respectively. Notably, the concentration of deoxynivalenol, a mycotoxin harmful to the health of humans and animals, was decreased in transgenic Arabidopsis siliques and maize seeds. This vesicle-mediated cell detoxification process provides a strategy to increase plant resistance against different toxin-associated diseases and to reduce the mycotoxin contamination in food and feed.
Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake
Authors: Zimoń Magdalena , Huang Yunfeng , Trasta Anthi , Halavatyi Aliaksandr , Liu Jimmy Z. , Chen Chia-Yen , Blattmann Peter , Klaus Bernd , Whelan Christopher D. , Sexton David , John Sally , Huber Wolfgang , Tsai Ellen A. , Pepperkok Rainer , Runz Heiko 
Published: November 2021

AbstractComplex traits are characterized by multiple genes and variants acting simultaneously on a phenotype. However, studying the contribution of individual pairs of genes to complex traits has been challenging since human genetics necessitates very large population sizes, while findings from model systems do not always translate to humans. Here, we combine genetics with combinatorial RNAi (coRNAi) to systematically test for pairwise additive effects (AEs) and genetic interactions (GIs) between 30 lipid genome-wide association studies (GWAS) genes. Gene-based burden tests from 240,970 exomes show that in carriers with truncating mutations in both,APOBand eitherPCSK9orLPL(“human double knock-outs”) plasma lipid levels change additively. Genetics and coRNAi identify overlapping AEs for 12 additional gene pairs. Overlapping GIs are observed forTOMM40/APOEwithSORT1andNCAN. Our study identifies distinct gene pairs that modulate plasma and cellular lipid levels primarily via AEs and nominates putative drug target pairs for improved lipid-lowering combination therapies.
Geometric characterization of anomalous Landau levels of isolated flat bands
Authors: Hwang Yoonseok , Rhim Jun-Won , Yang Bohm-Jung 
Published: November 2021

AbstractAccording to the Onsager’s semiclassical quantization rule, the Landau levels of a band are bounded by its upper and lower band edges at zero magnetic field. However, there are two notable systems where the Landau level spectra violate this expectation, including topological bands and flat bands with singular band crossings, whose wave functions possess some singularities. Here, we introduce a distinct class of flat band systems where anomalous Landau level spreading (LLS) appears outside the zero-field energy bounds, although the relevant wave function is nonsingular. The anomalous LLS of isolated flat bands are governed by the cross-gap Berry connection that measures the wave-function geometry of multi bands. We also find that symmetry puts strong constraints on the LLS of flat bands. Our work demonstrates that an isolated flat band is an ideal system for studying the fundamental role of wave-function geometry in describing magnetic responses of solids.