bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Interhemispheric Heat Transport and Global Atmospheric Cooling in Multidecadal Trends of Northern Hemisphere Precipitation
Authors: Yukimoto Seiji , Oshima Naga , Kawai Hideaki , Deushi Makoto , Aizawa Takuro 
Published: September 2022

AbstractChanges in the hydrological cycle in the northern hemisphere (NH) have a significant socioeconomic impact. Thus, quantifying past changes and projecting future changes in this cycle are important. We analyzed the positive and negative multidecadal trends in the NH mean precipitation since the 1950s that were accurately reproduced by a state‐of‐the‐art Earth system model. Results showed that changes in the interhemispheric heat transport play a major role in the NH atmospheric heat budget, accounting for 59% of the negative‐to‐positive trend change in NH precipitation through a north–south shift in the tropical precipitation zone, and were strongly linked to Hadley circulation anomaly. The remaining 41% corresponded to changes in atmospheric cooling with small interhemispheric differences, which were primarily related to clear‐sky longwave radiation. These findings quantitatively agreed with the results from a multimodel analysis.
Modulation of Atmospheric Rivers by the Arctic Stratospheric Polar Vortex
Authors: Lee Simon H. , Polvani Lorenzo M. , Guan Bin 
Published: September 2022

AbstractVariability in atmospheric river (AR) frequency can drive hydrometeorological extremes with broad societal impacts. Mitigating the impacts of increased or decreased AR frequency requires forewarning weeks to months ahead. A key driver of Northern Hemisphere wintertime mid‐latitude subseasonal‐to‐seasonal climate variability is the stratospheric polar vortex. Here, we quantify AR frequency, landfall, genesis, and termination depending on the strength of the lower stratospheric polar vortex. We find large differences between weak and strong vortex states consistent with a latitudinal shift of the eddy‐driven jet, with the greatest differences over the British Isles, Scandinavia, and Iberia. Significant differences are also found for the Pacific Northwest of North America. Most of the seasonal‐scale stratospheric modulation of precipitation over Europe is explained by modulation of ARs. Our results provide potentially useful statistics for extended‐range prediction, and highlight the importance of ARs in bringing about the precipitation response to anomalous vortex states.
Formation of Alfvén Wave Ducts by Magnetotail Flow Bursts
Authors: Yang Ziyi , Zhang Binzheng , Lotko William , Sorathia Kareem A. , Pham Kevin , Luan Xiaoli , Dou Xiankang , Lei Jiuhou 
Published: September 2022

AbstractGeomagnetic activity in Earth's outer magnetosphere stimulates intense and sometimes explosive flows of electromagnetic power propagating earthward as Alfvén waves. Observations show that among its various magnetospheric sources, Alfvénic Poynting flux from the magnetotail reaches the ionosphere with the greatest intensity. Dayside fluxes are statistically weaker though more persistent. Flankside fluxes are weakest. We show using global magnetohydrodynamic simulations that these distributions can be attributed to the formation (or not) of meridionally narrow, relatively uniform, low Alfvén conductance channels that efficiently transmit Alfvénic power to the near‐Earth space. These Alfvén ducts form naturally at the heads of flow bursts in the magnetotail but not in flankside flux tubes, where the transmission of Alfvénic power is strongly attenuated by reflections at large conductance gradients along the propagation path. The results elucidate the underlying physics that control efficient transmission of electromagnetic power from the magnetotail to low altitude to power Alfvénic aurora.
From bench to bedside: The mGluR5 system in people with and without Autism Spectrum Disorder and animal model systems
Authors: Carey Cornelia , Singh Nisha , Dunn Joel T. , Sementa Teresa , Mendez Maria Andreina , Velthuis Hester , Pereira Andreia C. , Pretzsch Charlotte Marie , Horder Jamie , Hader Stefan , Lythgoe David J. , Rotaru Diana-Georgina , Gee Anthony , Cash Diana , Veronese Mattia , Murphy Declan , McAlonan Grainne 
Published: September 2022

AbstractThe metabotropic glutamate receptor 5 (mGluR5) is a key regulator of excitatory (E) glutamate and inhibitory (I) γ-amino butyric acid (GABA) signalling in the brain. Despite the close functional ties between mGluR5 and E/I signalling, no-one has directly examined the relationship between mGluR5 and glutamate or GABA in vivo in the human brain of autistic individuals. We measured [18F] FPEB (18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile) binding in 15 adults (6 with Autism Spectrum Disorder) using two regions of interest, the left dorsomedial prefrontal cortex and a region primarily composed of left striatum and thalamus. These two regions were mapped out using MEGA-PRESS voxels and then superimposed on reconstructed PET images. This allowed for direct comparison between mGluR5, GABA + and Glx. To better understand the molecular underpinnings of our results we used an autoradiography study of mGluR5 in three mouse models associated with ASD:Cntnap2knockout,Shank3knockout, and16p11.2deletion. Autistic individuals had significantly higher [18F] FPEB binding (t(13) = −2.86,p = 0.047) in the left striatum/thalamus region of interest as compared to controls. Within this region, there was a strong negative correlation between GABA + and mGluR5 density across the entire cohort (Pearson’s correlation:r(14) = −0.763,p = 0.002).Cntnap2KO mice had significantly higher mGlu5 receptor binding in the striatum (caudate-putamen) as compared to wild-type (WT) mice (n = 15,p = 0.03). There were no differences in mGluR5 binding for mice with theShank3knockout or16p11.2deletion. Given thatCntnap2is associated with a specific striatal deficit of parvalbumin positive GABA interneurons and ‘autistic’ features, our findings suggest that an increase in mGluR5 in ASD may relate to GABAergic interneuron abnormalities.
Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis
Authors: Chen Yuyu , Wu Jinna , Zhang Shun , Gao Wenjie , Liao Zhiheng , Zhou Taifeng , Li Yongyong , Su Deying , Liu Hengyu , Yang Xiaoming , Su Peiqiang , Xu Caixia 
Published: September 2022

AbstractThe harmonious functioning of growth plate chondrocytes is crucial for skeletogenesis. These cells rely on an appropriate intensity of glycolysis to maintain survival and function in an avascular environment, but the underlying mechanism is poorly understood. Here we show that Hnrnpk orchestrates growth plate development by maintaining the appropriate intensity of glycolysis in chondrocytes. Ablating Hnrnpk causes the occurrence of dwarfism, exhibiting damaged survival and premature differentiation of growth plate chondrocytes. Furthermore, Hnrnpk deficiency results in enhanced transdifferentiation of hypertrophic chondrocytes and increased bone mass. In terms of mechanism, Hnrnpk binds toHif1amRNA and promotes its degradation. Deleting Hnrnpk upregulates the expression of Hif1α, leading to the increased expression of downstream glycolytic enzymes and then exorbitant glycolysis. Our study establishes an essential role of Hnrnpk in orchestrating the survival and differentiation of chondrocytes, regulating the Hif1α-glycolysis axis through a post-transcriptional mechanism during growth plate development.
Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors
Authors: Blümel Lena , Qin Nan , Berlandi Johannes , Paisana Eunice , Cascão Rita , Custódia Carlos , Pauck David , Picard Daniel , Langini Maike , Stühler Kai , Meyer Frauke-Dorothee , Göbbels Sarah , Malzkorn Bastian , Liebau Max C. , Barata João T. , Jeibmann Astrid , Kerl Kornelius , Erkek Serap , Kool Marcel , Pfister Stefan M. , Johann Pascal D. , Frühwald Michael C. , Borkhardt Arndt , Reifenberger Guido , Faria Claudia C. , Fischer Ute , Hasselblatt Martin , Bartl Jasmin , Remke Marc 
Published: September 2022

AbstractAtypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor in infants that is characterized by loss of nuclear expression of SMARCB1 or SMARCA4 proteins. Recent studies show that AT/RTs comprise three molecular subgroups, namely AT/RT-TYR, AT/RT-MYC and AT/RT-SHH. The subgroups show distinct expression patterns of genes involved in ciliogenesis, however, little is known about the functional roles of primary cilia in the biology of AT/RT. Here, we show that primary cilia are present across all AT/RT subgroups with specific enrichment in AT/RT-TYR patient samples. Furthermore, we demonstrate that primary ciliogenesis contributes to AT/RT biology in vitro and in vivo. Specifically, we observed a significant decrease in proliferation and clonogenicity following disruption of primary ciliogenesis in AT/RT cell line models. Additionally, apoptosis was significantly increased via the induction of STAT1 and DR5 signaling, as detected by proteogenomic profiling. In a Drosophila model of SMARCB1 deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with more than 20% of flies reaching adulthood. We also found significantly extended survival in an orthotopic xenograft mouse model of AT/RT upon disruption of primary ciliogenesis. Taken together, our findings indicate that primary ciliogenesis or its downstream signaling contributes to the aggressiveness of AT/RT and, therefore, may constitute a novel therapeutic target.
Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair
Authors: Audu Christopher O. , Melvin William J. , Joshi Amrita D. , Wolf Sonya J. , Moon Jadie Y. , Davis Frank M. , Barrett Emily C. , Mangum Kevin D. , Deng Hongping , Xing Xianying , Wasikowski Rachel , Tsoi Lam C. , Sharma Sriganesh B. , Bauer Tyler M. , Shadiow James , Corriere Matthew A. , Obi Andrea T. , Kunkel Steven L. , Levi Benjamin , Moore Bethany B. , Gudjonsson Johann E. , Smith Andrew M. , Gallagher Katherine A. 
Published: September 2022

AbstractMacrophage plasticity is critical for normal tissue repair following injury. In pathologic states such as diabetes, macrophage plasticity is impaired, and macrophages remain in a persistent proinflammatory state; however, the reasons for this are unknown. Here, using single-cell RNA sequencing of human diabetic wounds, we identified increased JMJD3 in diabetic wound macrophages, resulting in increased inflammatory gene expression. Mechanistically, we report that in wound healing, JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling. However, in the diabetic state, we found that IL-6, a cytokine increased in diabetic wound tissue at later time points post-injury, regulates JMJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism. Interestingly, RNA sequencing of wound macrophages isolated from mice with JMJD3-deficient myeloid cells (Jmjd3f/fLyz2Cre+) identified that the STING gene (Tmem173) is regulated by JMJD3 in wound macrophages. STING limits inflammatory cytokine production by wound macrophages during healing. However, in diabetic mice, its role changes to limit wound repair and enhance inflammation. This finding is important since STING is associated with chronic inflammation, and we found STING to be elevated in human and murine diabetic wound macrophages at late time points. Finally, we demonstrate that macrophage-specific, nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING. Taken together, this work highlights the central role of JMJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.
Black carbon and dust alter the response of mountain snow cover under climate change
Authors: Réveillet Marion , Dumont Marie , Gascoin Simon , Lafaysse Matthieu , Nabat Pierre , Ribes Aurélien , Nheili Rafife , Tuzet Francois , Ménégoz Martin , Morin Samuel , Picard Ghislain , Ginoux Paul 
Published: September 2022

AbstractBy darkening the snow surface, mineral dust and black carbon (BC) deposition enhances snowmelt and triggers numerous feedbacks. Assessments of their long-term impact at the regional scale are still largely missing despite the environmental and socio-economic implications of snow cover changes. Here we show, using numerical simulations, that dust and BC deposition advanced snowmelt by 17 ± 6 days on average in the French Alps and the Pyrenees over the 1979–2018 period. BC and dust also advanced by 10-15 days the peak melt water runoff, a substantial effect on the timing of water resources availability. We also demonstrate that the decrease in BC deposition since the 1980s moderates the impact of current warming on snow cover decline. Hence, accounting for changes in light-absorbing particles deposition is required to improve the accuracy of snow cover reanalyses and climate projections, that are crucial for better understanding the past and future evolution of mountain social-ecological systems.
Deciphering multi-way interactions in the human genome
Authors: Dotson Gabrielle A. , Chen Can , Lindsly Stephen , Cicalo Anthony , Dilworth Sam , Ryan Charles , Jeyarajan Sivakumar , Meixner Walter , Stansbury Cooper , Pickard Joshua , Beckloff Nicholas , Surana Amit , Wicha Max , Muir Lindsey A. , Rajapakse Indika 
Published: September 2022

AbstractChromatin architecture, a key regulator of gene expression, can be inferred using chromatin contact data from chromosome conformation capture, or Hi-C. However, classical Hi-C does not preserve multi-way contacts. Here we use long sequencing reads to map genome-wide multi-way contacts and investigate higher order chromatin organization in the human genome. We use hypergraph theory for data representation and analysis, and quantify higher order structures in neonatal fibroblasts, biopsied adult fibroblasts, and B lymphocytes. By integrating multi-way contacts with chromatin accessibility, gene expression, and transcription factor binding, we introduce a data-driven method to identify cell type-specific transcription clusters. We provide transcription factor-mediated functional building blocks for cell identity that serve as a global signature for cell types.
The AAA+ ATPase RavA and its binding partner ViaA modulate E. coli aminoglycoside sensitivity through interaction with the inner membrane
Authors: Felix Jan , Bumba Ladislav , Liesche Clarissa , Fraudeau Angélique , Rébeillé Fabrice , El Khoury Jessica Y. , Huard Karine , Gallet Benoit , Moriscot Christine , Kleman Jean-Philippe , Duhoo Yoan , Jessop Matthew , Kandiah Eaazhisai , Barras Frédéric , Jouhet Juliette , Gutsche Irina 
Published: September 2022

AbstractEnteric bacteria have to adapt to environmental stresses in the human gastrointestinal tract such as acid and nutrient stress, oxygen limitation and exposure to antibiotics. Membrane lipid composition has recently emerged as a key factor for stress adaptation. The E. coli ravA-viaA operon is essential for aminoglycoside bactericidal activity under anaerobiosis but its mechanism of action is unclear. Here we characterise the VWA domain-protein ViaA and its interaction with the AAA+ ATPase RavA, and find that both proteins localise at the inner cell membrane. We demonstrate that RavA and ViaA target specific phospholipids and subsequently identify their lipid-binding sites. We further show that mutations abolishing interaction with lipids restore induced changes in cell membrane morphology and lipid composition. Finally we reveal that these mutations render E. coli gentamicin-resistant under fumarate respiration conditions. Our work thus uncovers a ravA-viaA-based pathway which is mobilised in response to aminoglycosides under anaerobiosis and engaged in cell membrane regulation.
Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast
Authors: Geldhof Vincent , de Rooij Laura P. M. H. , Sokol Liliana , Amersfoort Jacob , De Schepper Maxim , Rohlenova Katerina , Hoste Griet , Vanderstichele Adriaan , Delsupehe Anne-Marie , Isnaldi Edoardo , Dai Naima , Taverna Federico , Khan Shawez , Truong Anh-Co K. , Teuwen Laure-Anne , Richard François , Treps Lucas , Smeets Ann , Nevelsteen Ines , Weynand Birgit , Vinckier Stefan , Schoonjans Luc , Kalucka Joanna , Desmedt Christine , Neven Patrick , Mazzone Massimiliano , Floris Giuseppe , Punie Kevin , Dewerchin Mieke , Eelen Guy , Wildiers Hans , Li Xuri , Luo Yonglun , Carmeliet Peter 
Published: September 2022

AbstractSince a detailed inventory of endothelial cell (EC) heterogeneity in breast cancer (BC) is lacking, here we perform single cell RNA-sequencing of 26,515 cells (including 8433 ECs) from 9 BC patients and compare them to published EC taxonomies from lung tumors. Angiogenic ECs are phenotypically similar, while other EC subtypes are different. Predictive interactome analysis reveals known but also previously unreported receptor-ligand interactions between ECs and immune cells, suggesting an involvement of breast EC subtypes in immune responses. We also identify a capillary EC subtype (LIPEC (Lipid Processing EC)), which expresses genes involved in lipid processing that are regulated by PPAR-γ and is more abundant in peri-tumoral breast tissue. Retrospective analysis of 4648 BC patients reveals that treatment with metformin (an indirect PPAR-γ signaling activator) provides long-lasting clinical benefit and is positively associated with LIPEC abundance. Our findings warrant further exploration of this LIPEC/PPAR-γ link for BC treatment.
QuasAr Odyssey: the origin of fluorescence and its voltage sensitivity in microbial rhodopsins
Authors: Silapetere Arita , Hwang Songhwan , Hontani Yusaku , Fernandez Lahore Rodrigo G. , Balke Jens , Escobar Francisco Velazquez , Tros Martijn , Konold Patrick E. , Matis Rainer , Croce Roberta , Walla Peter J. , Hildebrandt Peter , Alexiev Ulrike , Kennis John T. M. , Sun Han , Utesch Tillmann , Hegemann Peter 
Published: September 2022

AbstractRhodopsins had long been considered non-fluorescent until a peculiar voltage-sensitive fluorescence was reported for archaerhodopsin-3 (Arch3) derivatives. These proteins named QuasArs have been used for imaging membrane voltage changes in cell cultures and small animals. However due to the low fluorescence intensity, these constructs require use of much higher light intensity than other optogenetic tools. To develop the next generation of sensors, it is indispensable to first understand the molecular basis of the fluorescence and its modulation by the membrane voltage. Based on spectroscopic studies of fluorescent Arch3 derivatives, we propose a unique photo-reaction scheme with extended excited-state lifetimes and inefficient photoisomerization. Molecular dynamics simulations of Arch3, of the Arch3 fluorescent derivative Archon1, and of several its mutants have revealed different voltage-dependent changes of the hydrogen-bonding networks including the protonated retinal Schiff-base and adjacent residues. Experimental observations suggest that under negative voltage, these changes modulate retinal Schiff base deprotonation and promote a decrease in the populations of fluorescent species. Finally, we identified molecular constraints that further improve fluorescence quantum yield and voltage sensitivity.
Learning enhances encoding of time and temporal surprise in mouse primary sensory cortex
Authors: Rabinovich Rebecca J. , Kato Daniel D. , Bruno Randy M. 
Published: September 2022

AbstractPrimary sensory cortex has long been believed to play a straightforward role in the initial processing of sensory information. Yet, the superficial layers of cortex overall are sparsely active, even during sensory stimulation; additionally, cortical activity is influenced by other modalities, task context, reward, and behavioral state. Our study demonstrates that reinforcement learning dramatically alters representations among longitudinally imaged neurons in superficial layers of mouse primary somatosensory cortex. Learning an object detection task recruits previously unresponsive neurons, enlarging the neuronal population sensitive to touch and behavioral choice. Cortical responses decrease upon repeated stimulus presentation outside of the behavioral task. Moreover, training improves population encoding of the passage of time, and unexpected deviations in trial timing elicit even stronger responses than touches do. In conclusion, the superficial layers of sensory cortex exhibit a high degree of learning-dependent plasticity and are strongly modulated by non-sensory but behaviorally-relevant features, such as timing and surprise.
Structure of the PAPP-ABP5 complex reveals mechanism of substrate recognition
Authors: Judge Russell A. , Sridar Janani , Tunyasuvunakool Kathryn , Jain Rinku , Wang John C. K. , Ouch Christna , Xu Jun , Mafi Amirhossein , Nile Aaron H. , Remarcik Clint , Smith Corey L. , Ghosh Crystal , Xu Chen , Stoll Vincent , Jumper John , Singh Amoolya H. , Eaton Dan , Hao Qi 
Published: September 2022

AbstractInsulin-like growth factor (IGF) signaling is highly conserved and tightly regulated by proteases including Pregnancy-Associated Plasma Protein A (PAPP-A). PAPP-A and its paralog PAPP-A2 are metalloproteases that mediate IGF bioavailability through cleavage of IGF binding proteins (IGFBPs). Here, we present single-particle cryo-EM structures of the catalytically inactive mutant PAPP-A (E483A) in complex with a peptide from its substrate IGFBP5 (PAPP-ABP5) and also in its substrate-free form, by leveraging the power of AlphaFold to generate a high quality predicted model as a starting template. We show that PAPP-A is a flexible trans-dimer that binds IGFBP5 via a 25-amino acid anchor peptide which extends into the metalloprotease active site. This unique IGFBP5 anchor peptide that mediates the specific PAPP-A-IGFBP5 interaction is not found in other PAPP-A substrates. Additionally, we illustrate the critical role of the PAPP-A central domain as it mediates both IGFBP5 recognition and trans-dimerization. We further demonstrate that PAPP-A trans-dimer formation and distal inter-domain interactions are both required for efficient proteolysis of IGFBP4, but dispensable for IGFBP5 cleavage. Together the structural and biochemical studies reveal the mechanism of PAPP-A substrate binding and selectivity.
Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow
Authors: Shaw William M. , Zhang Yunfeng , Lu Xinyu , Khalil Ahmad S. , Ladds Graham , Luo Xiaozhou , Ellis Tom 
Published: September 2022

AbstractMicrobial production of cannabinoids promises to provide a consistent, cheaper, and more sustainable supply of these important therapeutic molecules. However, scaling production to compete with traditional plant-based sources is challenging. Our ability to make strain variants greatly exceeds our capacity to screen and identify high producers, creating a bottleneck in metabolic engineering efforts. Here, we present a yeast-based biosensor for detecting microbially produced Δ9-tetrahydrocannabinol (THC) to increase throughput and lower the cost of screening. We port five human cannabinoid G protein-coupled receptors (GPCRs) into yeast, showing the cannabinoid type 2 receptor, CB2R, can couple to the yeast pheromone response pathway and report on the concentration of a variety of cannabinoids over a wide dynamic and operational range. We demonstrate that our cannabinoid biosensor can detect THC from microbial cell culture and use this as a tool for measuring relative production yields from a library of Δ9-tetrahydrocannabinol acid synthase (THCAS) mutants.