bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signature of Sudden Stratospheric Warming in the Pole and Its Antipode
Authors: Dutta Reetambhara , Sridharan S. , Sinha P. R. 
Published: February 2024

AbstractIn this study, the boreal sudden stratospheric warming (SSW) event of 2013 and the austral SSW event of 2019 are considered to investigate the influence of the SSW events on the polar and antipodal upper mesosphere and lower thermosphere (UMLT) regions using ground‐based, space‐borne, reanalysis and model data sets. During the SSW events, the solar semi‐diurnal tidal (SDT) amplitudes are much larger than the lunar amplitudes in both UMLT regions. Besides, the solar SDT shows an increase in its amplitude in both the polar UMLT heights during the SSW events. However, the lunar tides show enhancement in its amplitude in the boreal polar UMLT region during both the SSW events. In the antipodal UMLT region, a peak enhancement in solar SDT amplitude is observed a few days after the onset of the boreal SSW and near to the onset time of the austral SSW. No concurrent stratospheric ozone volume mixing ratio (vmr) increase is observed which indicates that the SDT peak can be unlikely due to the underlying stratospheric ozone vmr changes. However, similar periodicity in the UMLT zonal winds of both poles indicates the possibility of cross equatorial propagation of planetary wave (PW). As the SDT amplitude also reveal similar planetary wave periodicity as observed in zonal wind, it is suggested that the PW modulation of the SDT could be the reason for the enhancement of SDT in the opposite polar UMLT region.
Physical and Biogeochemical Properties of California Current Upwelled Source Waters
Authors: Fiechter Jerome , Moore Andrew M. 
Published: February 2024

AbstractCoastal upwelling variability in the California Current region, one of the four main eastern boundary current upwelling systems, is controlled by processes acting over a wide range of spatial and temporal scales. While the ensuing ecosystem response depends strongly on upwelled water properties, determining their exact physical and biogeochemical characteristics is notoriously difficult as it requires tracking water masses backward in space and time from the moment they upwell near the coast to their subsurface origin. Adjoint model simulations have been used successfully to track water masses in coastal upwelling systems and the work presented here extends these applications to determining the co‐variability of physical and biogeochemical properties of source waters at spatial scales that resolve the known alongshore variability of coastal upwelling in the region. Notably, the results identify that the modulation of coastal upwelling efficiency by onshore/offshore geostrophic meanders is the dominant mechanism explaining alongshore variability in source depth and properties of upwelled waters. The simulations also reveal that source water properties vary seasonally in response to different balances between coastal upwelling intensity and biogeochemical processes. During spring, interannual variability of physical and biogeochemical properties is directly tied to the intensity of upwelling‐favorable alongshore winds, whereas, during summer, biogeochemical properties respond more strongly to biological activity and subsequent organic matter remineralization at depth. Overall, the present work provides important insight into the mechanisms responsible for the alongshore mosaic and seasonal variation of upwelled source water properties in the central California Current region.
Evolution of Impact Melt Pools on Titan
Authors: Kalousová Klára , Wakita Shigeru , Sotin Christophe , Neish Catherine D. , Soderblom Jason M. , Souček Ondřej , Johnson Brandon C. 
Published: February 2024

AbstractTitan is an ocean world with a dense atmosphere, where photochemistry produces complex organic molecules that fall to the surface. An important astrobiological question is whether this material can mix with water and form molecules of biological interest. Large impacts heat the moon's subsurface and create liquid water melt pools. A recent study investigated impacts into Titan's clathrate‐covered ice shell. Methane clathrates are stable at Titan's surface conditions and have low thermal conductivity, making them efficient insulators that can lead to steep thermal gradients and a thin stagnant lid. The authors showed that the clathrate layer thickness primarily influences the melt distribution, while its volume is governed by the impactor size. Here, we investigate the fate of melt formed during an impact into a clathrate‐covered ice shell. Our results show two different behaviors: in cases when less melt is produced, the subsurface melt pool remains close to the surface and freezes on timescales ≲25 kyr; in cases when larger volumes of melt are produced, a downward‐oriented transport of the molten material occurs. As it descends, part of the melt freezes but some may reach the ocean within a few kyr under certain conditions; vertical impacts, high surface porosity, low viscosity, and tidal heating all favor this surface‐to‐ocean exchange. While providing insights on parameters that allow a subsurface melt pool to remain liquid beneath a Selk‐sized crater for a few kyr, this study suggests that Dragonfly may be able to sample melt deposits where organics reacted with liquid water to produce biomolecules.
Quantification of the Airborne Fraction of Atmospheric CO2 Reveals Stability in Global Carbon Sinks Over the Past Six Decades
Authors: Bennett Brian F. , Salawitch Ross J. , McBride Laura A. , Hope Austin P. , Tribett Walter R. 
Published: February 2024

AbstractThe airborne fraction of atmospheric CO2 (AF), defined as the annual global CO2 growth rate (dCO2/dt) divided by the total emission of CO2 from combustion of fossil fuels and land use change (LUC), has a long‐term average of ∼0.44 over the past six decades. When quantifying trends in AF it is important to account for inter‐annual variability in dCO2/dt due to natural factors such as the El Niño Southern Oscillation (ENSO) and major volcanic eruptions, as well as assumptions regarding LUC. Here, a multiple linear regression model is used to compute dCO2/dt as a function of anthropogenic CO2 emissions, ENSO indices, and stratospheric aerosol optical depth (a proxy for major volcanic eruptions), for numerous time series of the emission of CO2 due to LUC (ELUC). For 20 out of 21 previously published ELUC time series, the trend in AF adjusted for natural variability (AFADJ) over 1959 to 2021 exhibits a trend that is statistically indistinguishable from zero and lacks statistical significance at the 95% confidence interval. Therefore, it is most likely that the relative efficacy of the combined global terrestrial biosphere and oceanic carbon sinks has been fairly constant on a global scale over the past six decades. Since the trend in AF exhibits considerable variability depending on which ELUC time series is used, more precise knowledge of the actual value of the AF trend will require resolving the current large differences in various estimates of ELUC.
Nightmares share genetic risk factors with sleep and psychiatric traits
Authors: Ollila Hanna M. , Sinnott-Armstrong Nasa , Kantojärvi Katri , Broberg Martin , Palviainen Teemu , Jones Samuel , Ripatti Vili , Pandit Anita , Rong Robin , Kristiansson Kati , Sandman Nils , Valli Katja , Hublin Christer , Ripatti Samuli , Widen Elisabeth , Kaprio Jaakko , Saxena Richa , Paunio Tiina 
Published: February 2024

AbstractNightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e−06), depressive (rg = 0.562, p = 1.282e−07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e−07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual’s liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts.
KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC
Authors: Li Jinghan , Shi Daiwang , Li Siyi , Shi Xiang , Liu Yu , Zhang Yi , Wang Gebang , Zhang Chenlei , Xia Tian , Piao Hai-long , Liu Hong-Xu 
Published: February 2024

AbstractImmunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.
SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation
Authors: Nashabat Marwan , Nabavizadeh Nasrinsadat , Saraçoğlu Hilal Pırıl , Sarıbaş Burak , Avcı Şahin , Börklü Esra , Beillard Emmanuel , Yılmaz Elanur , Uygur Seyide Ecesu , Kayhan Cavit Kerem , Bosco Luca , Eren Zeynep Bengi , Steindl Katharina , Richter Manuela Friederike , Bademci Guney , Rauch Anita , Fattahi Zohreh , Valentino Maria Lucia , Connolly Anne M. , Bahr Angela , Viola Laura , Bergmann Anke Katharina , Rocha Maria Eugenia , Peart LeShon , Castro-Rojas Derly Liseth , Bültmann Eva , Khan Suliman , Giarrana Miriam Liliana , Teleanu Raluca Ioana , Gonzalez Joanna Michelle , Pini Antonella , Schädlich Ines Sophie , Vill Katharina , Brugger Melanie , Zuchner Stephan , Pinto Andreia , Donkervoort Sandra , Bivona Stephanie Ann , Riza Anca ,   Undiagnosed Diseases Network, Zuchner Stephan , Tekin Mustafa , Streata Ioana , Gläser Dieter , Baquero-Montoya Carolina , Garcia-Restrepo Natalia , Kotzaeridou Urania , Brunet Theresa , Epure Diana Anamaria , Bertoli-Avella Aida , Kariminejad Ariana , Tekin Mustafa , von Hardenberg Sandra , Bönnemann Carsten G. , Stettner Georg M. , Zanni Ginevra , Kayserili Hülya , Oflazer Zehra Piraye , Escande-Beillard Nathalie 
Published: February 2024

AbstractSNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.
Comparative connectomics of dauer reveals developmental plasticity
Authors: Yim Hyunsoo , Choe Daniel T. , Bae J. Alexander , Choi Myung-kyu , Kang Hae-Mook , Nguyen Ken C. Q. , Ahn Soungyub , Bahn Sang-kyu , Yang Heeseung , Hall David H. , Kim Jinseop S. , Lee Junho 
Published: February 2024

AbstractA fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the chemical connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode has evolved to respond to harsh environments by developing a quantitatively and qualitatively differentiated connectome.
TopBP1 utilises a bipartite GINS binding mode to support genome replication
Authors: Day Matthew , Tetik Bilal , Parlak Milena , Almeida-Hernández Yasser , Räschle Markus , Kaschani Farnusch , Siegert Heike , Marko Anika , Sanchez-Garcia Elsa , Kaiser Markus , Barker Isabel A. , Pearl Laurence H. , Oliver Antony W. , Boos Dominik 
Published: February 2024

AbstractActivation of the replicative Mcm2-7 helicase by loading GINS and Cdc45 is crucial for replication origin firing, and as such for faithful genetic inheritance. Our biochemical and structural studies demonstrate that the helicase activator GINS interacts with TopBP1 through two separate binding surfaces, the first involving a stretch of highly conserved amino acids in the TopBP1-GINI region, the second a surface on TopBP1-BRCT4. The two surfaces bind to opposite ends of the A domain of the GINS subunit Psf1. Mutation analysis reveals that either surface is individually able to support TopBP1-GINS interaction, albeit with reduced affinity. Consistently, either surface is sufficient for replication origin firing in Xenopus egg extracts and becomes essential in the absence of the other. The TopBP1-GINS interaction appears sterically incompatible with simultaneous binding of DNA polymerase epsilon (Polε) to GINS when bound to Mcm2-7-Cdc45, although TopBP1-BRCT4 and the Polε subunit PolE2 show only partial competitivity in binding to Psf1. Our TopBP1-GINS model improves the understanding of the recently characterised metazoan pre-loading complex. It further predicts the coordination of three molecular origin firing processes, DNA polymerase epsilon arrival, TopBP1 ejection and GINS integration into Mcm2-7-Cdc45.
scCircle-seq unveils the diversity and complexity of extrachromosomal circular DNAs in single cells
Authors: Chen Jinxin Phaedo , Diekmann Constantin , Wu Honggui , Chen Chong , Della Chiara Giulia , Berrino Enrico , Georgiadis Konstantinos L. , Bouwman Britta A. M. , Virdi Mohit , Harbers Luuk , Bellomo Sara Erika , Marchiò Caterina , Bienko Magda , Crosetto Nicola 
Published: February 2024

AbstractExtrachromosomal circular DNAs (eccDNAs) have emerged as important intra-cellular mobile genetic elements that affect gene copy number and exert in trans regulatory roles within the cell nucleus. Here, we describe scCircle-seq, a method for profiling eccDNAs and unraveling their diversity and complexity in single cells. We implement and validate scCircle-seq in normal and cancer cell lines, demonstrating that most eccDNAs vary largely between cells and are stochastically inherited during cell division, although their genomic landscape is cell type-specific and can be used to accurately cluster cells of the same origin. eccDNAs are preferentially produced from chromatin regions enriched in H3K9me3 and H3K27me3 histone marks and are induced during replication stress conditions. Concomitant sequencing of eccDNAs and RNA from the same cell uncovers the absence of correlation between eccDNA copy number and gene expression levels, except for a few oncogenes, including MYC, contained within a large eccDNA in colorectal cancer cells. Lastly, we apply scCircle-seq to one prostate cancer and two breast cancer specimens, revealing cancer-specific eccDNA landscapes and a higher propensity of eccDNAs to form in amplified genomic regions. scCircle-seq is a scalable tool that can be used to dissect the complexity of eccDNAs across different cell and tissue types, and further expands the potential of eccDNAs for cancer diagnostics.
How heat propagates in liquid 3He
Authors: Behnia Kamran , Trachenko Kostya 
Published: February 2024

AbstractIn Landau’s Fermi liquid picture, transport is governed by scattering between quasi-particles. The normal liquid 3He conforms to this picture but only at very low temperature. Here, we show that the deviation from the standard behavior is concomitant with the fermion-fermion scattering time falling below the Planckian time, $$\frac{\hslash }{{k}_{{{{{{{{\rm{B}}}}}}}}}T}$$

ℏ

k

B

T

and the thermal diffusivity of this quantum liquid is bounded by a minimum set by fundamental physical constants and observed in classical liquids. This points to collective excitations (a sound mode) as carriers of heat. We propose that this mode has a wavevector of 2kF and a mean free path equal to the de Broglie thermal length. This would provide an additional conducting channel with a T 1/2 temperature dependence, matching what is observed by experiments. The experimental data from 0.007 K to 3 K can be accounted for, with a margin of 10%, if thermal conductivity is the sum of two contributions: one by quasi-particles (varying as the inverse of temperature) and another by sound (following the square root of temperature).
Accelerated elastin degradation by age-disease interaction: a common feature in age-related diseases
Authors: Shek Naomi , Choy Anna-Maria , Lang Chim C. , Miller Bruce E. , Tal-Singer Ruth , Bolton Charlotte E. , Thomson Neil C. , Chalmers James D. , Bown Matt J. , Newby David E. , Khan Faisel , Huang Jeffrey T. J. 
Published: February 2024

AbstractAging is a major driving force for many diseases but the relationship between chronological age, the aging process and age-related diseases is not fully understood. Fragmentation and loss of ultra-long-lived elastin are key features in aging and several age-related diseases leading to increased mortality. By comparing the relationship between age and elastin turnover with healthy volunteers, we show that accelerated elastin turnover by age-disease interaction is a common feature of age-related diseases.
Thwarting resistance: MgrA inhibition with methylophiopogonanone a unveils a new battlefront against S. aureus
Authors: Guo Xuerui , Wang Li , Zhang Jinlong , Liu Quan , Wang Bingmei , Liu Da , Gao Fei , Lanzi Gongga , Zhao Yicheng , Shi Yan 
Published: February 2024

AbstractLimitations in the clinical treatment of Staphylococcus aureus (S. aureus) infections have arisen due to the advent of antibiotic-resistant strains. Given the immense potential of therapeutic strategies targeting bacterial virulence, the role of MgrA as a pivotal virulence determinant in S. aureus-orchestrating resistance, adherence, and hundreds of virulence targets—becomes indispensable. In this investigation, leveraging advanced virtual screening and fluorescence anisotropy assays, we discerned methylophiopogonanone A (Mo-A), a flavonoid derivative, as a potent disruptor of the MgrA-DNA interaction nexus. Subsequent analysis revealed that Mo-A effectively inhibits the expression of virulence factors such as Hla and Pvl in S. aureus and markedly reduces its adhesion capability to fibrinogen. On a cellular landscape, Mo-A exerts a mitigating influence on the deleterious effects inflicted by S. aureus USA300 on A549 cells. Furthermore, our data indicate that Mo-A downregulates the transcription of genes associated with immune evasion, such as nucleases (nuc), Staphylococcal Chemotaxis Inhibitory Protein (chips), and Staphylococcal Complement Inhibitor (scin), thereby undermining immune escape and amplifying neutrophil chemotaxis. Upon application in an in vivo setting, Mo-A assumes a protective persona in a murine model of S. aureus USA300-induced pneumonia and demonstrates efficacy in the Galleria mellonella infection model. Of note, S. aureus displayed no swift acquisition of resistance to Mo-A, and the effect was synergistically enhanced when used in combination with vancomycin. Our findings add substantive weight to the expanding field of virulence-targeted therapeutic strategies and set the stage for more comprehensive exploration of Mo-A potential in combating antibiotic-resistant S. aureus.
Linking cerebral hemodynamics and ocular microgravity-induced alterations through an in silico-in vivo head-down tilt framework
Authors: Fois Matteo , Diaz-Artiles Ana , Zaman Syeda Yasmin , Ridolfi Luca , Scarsoglio Stefania 
Published: February 2024

AbstractHead-down tilt (HDT) has been widely proposed as a terrestrial analog of microgravity and used also to investigate the occurrence of spaceflight-associated neuro-ocular syndrome (SANS), which is currently considered one of the major health risks for human spaceflight. We propose here an in vivo validated numerical framework to simulate the acute ocular-cerebrovascular response to 6° HDT, to explore the etiology and pathophysiology of SANS. The model links cerebral and ocular posture-induced hemodynamics, simulating the response of the main cerebrovascular mechanisms, as well as the relationship between intracranial and intraocular pressure to HDT. Our results from short-term (10 min) 6° HDT show increased hemodynamic pulsatility in the proximal-to-distal/capillary-venous cerebral direction, a marked decrease (-43%) in ocular translaminar pressure, and an increase (+31%) in ocular perfusion pressure, suggesting a plausible explanation of the underlying mechanisms at the onset of ocular globe deformation and edema formation over longer time scales.