bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNF8 enhances the sensitivity of PD-L1 inhibitor against melanoma through ubiquitination of galectin-3 in stroma
Authors: Guo Yanan , Shen Rong , Yang Keren , Wang Yutong , Song Haoyun , Liu Xiangwen , Cheng Xin , Wu Rile , Song Yanfeng , Wang Degui 
Published: June 2023

AbstractThe failure of melanoma immunotherapy can be mediated by immunosuppression in the tumor microenvironment (TME), and insufficient activation of effector T cells against the tumor. Here, we show that inhibition of galectin-3 (gal-3) enhances the infiltration of T cells in TME and improves the sensitivity of anti-PD-L1 therapy. We identify that RNF8 downregulated the expression of gal-3 by K48-polyubiquitination and promoted gal-3 degradation via the ubiquitin–proteasome system. RNF8 deficiency in the host but sufficiency in implanted melanoma results in immune exclusion and tumor progression due to the upregulation of gal-3. Upregulation of gal-3 decreased the immune cell infiltration by restricting IL-12 and IFN-γ. Inhibition of gal-3 reverses immunosuppression and induces immune cell infiltration in the tumor microenvironment. Moreover, gal-3 inhibitor treatment can increase the sensitivity of PD-L1 inhibitors via increasing immune cell infiltration and enhancing immune response in tumors. This study reveals a previously unrecognized immunoregulation function of RNF8 and provides a promising strategy for the therapy of “cold” tumors. Tremendous effects of melanoma treatment can be achieved by facilitating immune cell infiltration combined with anti-PD-L1 treatment.
Foreshock properties illuminate nucleation processes of slow and fast laboratory earthquakes
Authors: Bolton David C. , Marone Chris , Saffer Demian , Trugman Daniel T. 
Published: June 2023

AbstractUnderstanding the connection between seismic activity and the earthquake nucleation process is a fundamental goal in earthquake seismology with important implications for earthquake early warning systems and forecasting. We use high-resolution acoustic emission (AE) waveform measurements from laboratory stick-slip experiments that span a spectrum of slow to fast slip rates to probe spatiotemporal properties of laboratory foreshocks and nucleation processes. We measure waveform similarity and pairwise differential travel-times (DTT) between AEs throughout the seismic cycle. AEs broadcasted prior to slow labquakes have small DTT and high waveform similarity relative to fast labquakes. We show that during slow stick-slip, the fault never fully locks, and waveform similarity and pairwise differential travel times do not evolve throughout the seismic cycle. In contrast, fast laboratory earthquakes are preceded by a rapid increase in waveform similarity late in the seismic cycle and a reduction in differential travel times, indicating that AEs begin to coalesce as the fault slip velocity increases leading up to failure. These observations point to key differences in the nucleation process of slow and fast labquakes and suggest that the spatiotemporal evolution of laboratory foreshocks is linked to fault slip velocity.
Robust projection of East Asian summer monsoon rainfall based on dynamical modes of variability
Authors: Xue Daokai , Lu Jian , Leung L. Ruby , Teng Haiyan , Song Fengfei , Zhou Tianjun , Zhang Yaocun 
Published: June 2023

AbstractThe Asian monsoon provides the freshwater that a large population in Asia depends on, but how anthropogenic climate warming may alter this key water source remains unclear. This is partly due to the prevailing point-wise assessment of climate projections, even though climate change patterns are inherently organized by dynamics intrinsic to the climate system. Here, we assess the future changes in the East Asian summer monsoon precipitation by projecting the precipitation from several large ensemble simulations and CMIP6 simulations onto the two leading dynamical modes of internal variability. The result shows a remarkable agreement among the ensembles on the increasing trends and the increasing daily variability in both dynamical modes, with the projection pattern emerging as early as the late 2030 s. The increase of the daily variability of the modes heralds more monsoon-related hydrological extremes over some identifiable East Asian regions in the coming decades.
Magmatic surge requires two-stage model for the Laramide orogeny
Authors: Schwartz Joshua J. , Lackey Jade Star , Miranda Elena A. , Klepeis Keith A. , Mora-Klepeis Gabriela , Robles Francine , Bixler Jonathan D. 
Published: June 2023

AbstractThe Laramide orogeny is a pivotal time in the geological development of western North America, but its driving mechanism is controversial. Most prominent models suggest this event was caused by the collision of an oceanic plateau with the Southern California Batholith (SCB) which caused the angle of subduction beneath the continent to shallow and led to shut-down of the arc. Here, we use over 280 zircon and titanite Pb/U ages from the SCB to establish the timing and duration of magmatism, metamorphism and deformation. We show that magmatism was surging in the SCB from 90 to 70 Ma, the lower crust was hot, and cooling occurred after 75 Ma. These data contradict plateau underthrusting and flat-slab subduction as the driving mechanism for early Laramide deformation. We propose that the Laramide orogeny is a two-stage event consisting of: 1) an arc ‘flare-up’ phase in the SCB from 90-75 Ma; and 2) a widespread mountain building phase in the Laramide foreland belt from 75-50 Ma that is linked to subduction of an oceanic plateau.
Learning-induced reorganization of number neurons and emergence of numerical representations in a biologically inspired neural network
Authors: Mistry Percy K. , Strock Anthony , Liu Ruizhe , Young Griffin , Menon Vinod 
Published: June 2023

AbstractNumber sense, the ability to decipher quantity, forms the foundation for mathematical cognition. How number sense emerges with learning is, however, not known. Here we use a biologically-inspired neural architecture comprising cortical layers V1, V2, V3, and intraparietal sulcus (IPS) to investigate how neural representations change with numerosity training. Learning dramatically reorganized neuronal tuning properties at both the single unit and population levels, resulting in the emergence of sharply-tuned representations of numerosity in the IPS layer. Ablation analysis revealed that spontaneous number neurons observed prior to learning were not critical to formation of number representations post-learning. Crucially, multidimensional scaling of population responses revealed the emergence of absolute and relative magnitude representations of quantity, including mid-point anchoring. These learnt representations may underlie changes from logarithmic to cyclic and linear mental number lines that are characteristic of number sense development in humans. Our findings elucidate mechanisms by which learning builds novel representations supporting number sense.
Machining water through laser cutting of nanoparticle-encased water pancakes
Authors: Niu Jicheng , Liu Wenjing , Li Jasmine Xinze , Pang Xianglong , Liu Yulin , Zhang Chao , Yue Keyang , Zhou Yulin , Xu Feng , Li Xiaoguang , Li Fei 
Published: June 2023

AbstractDue to the inherent disorder and fluidity of water, precise machining of water through laser cutting are challenging. Herein we report a strategy that realizes the laser cutting machining of water through constructing hydrophobic silica nanoparticle-encased water pancakes with sub-millimeter depth. Through theoretical analysis, numerical simulation, and experimental studies, the developed process of nanoparticle-encased water pancake laser cutting and the parameters that affect cutting accuracy are verified and elucidated. We demonstrate that laser-fabricated water patterns can form diverse self-supporting chips (SSCs) with openness, transparency, breathability, liquid morphology, and liquid flow control properties. Applications of laser-fabricated SSCs to various fields, including chemical synthesis, biochemical sensing, liquid metal manipulation, patterned hydrogel synthesis, and drug screening, are also conceptually demonstrated. This work provides a strategy for precisely machining water using laser cutting, addressing existing laser machining challenges and holding significance for widespread fields involving fluid patterning and flow control in biological, chemical, materials and biomedical research.
Immunological imprinting of humoral immunity to SARS-CoV-2 in children
Authors: Dowell Alexander C. , Lancaster Tara , Bruton Rachel , Ireland Georgina , Bentley Christopher , Sylla Panagiota , Zuo Jianmin , Scott Sam , Jadir Azar , Begum Jusnara , Roberts Thomas , Stephens Christine , Ditta Shabana , Shepherdson Rebecca , Powell Annabel A. , Brent Andrew J. , Brent Bernadette , Baawuah Frances , Okike Ifeanyichukwu , Beckmann Joanne , Ahmad Shazaad , Aiano Felicity , Garstang Joanna , Ramsay Mary E. , Azad Rafaq , Waiblinger Dagmar , Willett Brian , Wright John , Ladhani Shamez N. , Moss Paul 
Published: June 2023

AbstractOmicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.
Glacier retreat alters downstream fjord ecosystem structure and function in Greenland
Authors: Meire Lorenz , Paulsen Maria Lund , Meire Patrick , Rysgaard Søren , Hopwood Mark James , Sejr Mikael Kristian , Stuart-Lee Alice , Sabbe Koen , Stock Willem , Mortensen John 
Published: June 2023

AbstractThe melting of the Greenland Ice Sheet is accelerating, with glaciers shifting from marine to land termination and potential consequences for fjord ecosystems downstream. Monthly samples in 2016 in two fjords in southwest Greenland show that subglacial discharge from marine-terminating glaciers sustains high phytoplankton productivity that is dominated by diatoms and grazed by larger mesozooplankton throughout summer. In contrast, melting of land-terminating glaciers results in a fjord ecosystem dominated by bacteria, picophytoplankton and smaller zooplankton, which has only one-third of the annual productivity and half the CO2 uptake compared to the fjord downstream from marine-terminating glaciers.
The TNFR1 antagonist Atrosimab reduces neuronal loss, glial activation and memory deficits in an acute mouse model of neurodegeneration
Authors: Ortí-Casañ Natalia , Boerema Ate S. , Köpke Karina , Ebskamp Amber , Keijser Jan , Zhang Yuequ , Chen Tingting , Dolga Amalia M. , Broersen Kerensa , Fischer Roman , Pfizenmaier Klaus , Kontermann Roland E. , Eisel Ulrich L. M. 
Published: June 2023

AbstractTumor necrosis factor alpha (TNF-α) and its key role in modulating immune responses has been widely recognized as a therapeutic target for inflammatory and neurodegenerative diseases. Even though inhibition of TNF-α is beneficial for the treatment of certain inflammatory diseases, total neutralization of TNF-α largely failed in the treatment of neurodegenerative diseases. TNF-α exerts distinct functions depending on interaction with its two TNF receptors, whereby TNF receptor 1 (TNFR1) is associated with neuroinflammation and apoptosis and TNF receptor 2 (TNFR2) with neuroprotection and immune regulation. Here, we investigated the effect of administering the TNFR1-specific antagonist Atrosimab, as strategy to block TNFR1 signaling while maintaining TNFR2 signaling unaltered, in an acute mouse model for neurodegeneration. In this model, a NMDA-induced lesion that mimics various hallmarks of neurodegenerative diseases, such as memory loss and cell death, was created in the nucleus basalis magnocellularis and Atrosimab or control protein was administered centrally. We showed that Atrosimab attenuated cognitive impairments and reduced neuroinflammation and neuronal cell death. Our results demonstrate that Atrosimab is effective in ameliorating disease symptoms in an acute neurodegenerative mouse model. Altogether, our study indicates that Atrosimab may be a promising candidate for the development of a therapeutic strategy for the treatment of neurodegenerative diseases.
Reduction in sugar drink valuation and consumption with gamified executive control training
Authors: Najberg Hugo , Mouthon Michael , Coppin Géraldine , Spierer Lucas 
Published: June 2023

AbstractThe overvaluation of high-energy, palatable food cues contributes to unhealthy eating and being overweight. Reducing the valuation of unhealthy food may thus constitute a powerful lever to improve eating habits and conditions characterized by unhealthy eating. We conducted a double-blind, placebo-controlled, randomized intervention trial assessing the efficacy of a five to twenty days online cognitive training intervention to reduce sugary drink perceived palatability and consumption. Our intervention involved a recently identified action-to-valuation mechanism of action, in which the repeated inhibition of prepotent motor responses to hedonic food cues in a Go/NoGo (GNG) and an attentional bias modification (ABM) task eventually reduces their valuation and intake. Confirming our hypotheses, the experimental intervention with consistent (100%) mapping between motor inhibition and the targeted unhealthy sugary drinks cues induced a larger decrease in their valuation than the control intervention with inconsistent (50%) mapping (− 27.6% vs. − 19%), and a larger increase of the (water) items associated with response execution (+ 11% vs + 4.2%). Exploratory analyses suggest that the effect of training on unhealthy items valuation may persist for at least one month. Against our hypothesis, we observed equivalent reductions in self-reported consumption of sugary drinks following the two interventions (exp: − 27% vs. ctrl: − 19%, BF01 = 4.7), suggesting a dose-independent effect of motor inhibition on self-reported consumption. Our collective results corroborate the robustness and large size of the devaluation effects induced by response inhibition on palatable items, but challenge the assumption of a linear relationship between such effects and the actual consumption of the target items.Protocol registrationThe stage 1 protocol for this Registered Report was accepted in principle on 30/03/2021. The protocol, as accepted by the journal, can be found at:https://doi.org/10.17605/OSF.IO/5ESMP.
MDTOMO method for continuous conformational variability analysis in cryo electron subtomograms based on molecular dynamics simulations
Authors: Vuillemot Rémi , Rouiller Isabelle , Jonić Slavica 
Published: June 2023

AbstractCryo electron tomography (cryo-ET) allows observing macromolecular complexes in their native environment. The common routine of subtomogram averaging (STA) allows obtaining the three-dimensional (3D) structure of abundant macromolecular complexes, and can be coupled with discrete classification to reveal conformational heterogeneity of the sample. However, the number of complexes extracted from cryo-ET data is usually small, which restricts the discrete-classification results to a small number of enough populated states and, thus, results in a largely incomplete conformational landscape. Alternative approaches are currently being investigated to explore the continuity of the conformational landscapes that in situ cryo-ET studies could provide. In this article, we present MDTOMO, a method for analyzing continuous conformational variability in cryo-ET subtomograms based on Molecular Dynamics (MD) simulations. MDTOMO allows obtaining an atomic-scale model of conformational variability and the corresponding free-energy landscape, from a given set of cryo-ET subtomograms. The article presents the performance of MDTOMO on a synthetic ABC exporter dataset and an in situ SARS-CoV-2 spike dataset. MDTOMO allows analyzing dynamic properties of molecular complexes to understand their biological functions, which could also be useful for structure-based drug discovery.
Role of immigration and emigration on the spread of COVID-19 in a multipatch environment: a case study of India
Authors: Das Tanuja , Bandekar Shraddha Ramdas , Srivastav Akhil Kumar , Srivastava Prashant K , Ghosh Mini 
Published: June 2023

AbstractHuman mobility has played a critical role in the spread of COVID-19. The understanding of mobility helps in getting information on the acceleration or control of the spread of disease. The COVID-19 virus has been spreading among several locations despite all the best efforts related to its isolation. To comprehend this, a multi-patch mathematical model of COVID-19 is proposed and analysed in this work, where-in limited medical resources, quarantining, and inhibitory behaviour of healthy individuals are incorporated into the model. Furthermore, as an example, the impact of mobility in a three-patch model is studied considering the three worst-hit states of India, i.e. Kerala, Maharashtra and Tamil Nadu, as three patches. Key parameters and the basic reproduction number are estimated from the available data. Through results and analyses, it is seen that Kerala has a higher effective contact rate and has the highest prevalence. Moreover, if Kerala is isolated from Maharashtra or Tamil Nadu, the number of active cases will increase in Kerala but reduce in the other two states. Our findings indicate that the number of active cases will decrease in the high prevalence state and increase in the lower prevalence states if the emigration rate is higher than the immigration rate in the high prevalence state. Overall, proper travel restrictions are to be implemented to reduce or control the spread of disease from the high-prevalence state to other states with lower prevalence rates.
Preparation 2-hydroxy-1-naphthaldehyde cross-linked Fe3O4@chitosan-polyacrylamide nanocomposite for removal of everzol black from aqueous solutions
Authors: Saadat Afshin , Banaei Alireza , Sattarifar Mehdi , Pargolghasemi Parinaz 
Published: June 2023

AbstractIn this study, new 2-hydroxy-1-naphthaldehyde linked Fe3O4/chitosan-polyacrylamide nanocomposite (Fe3O4@CS@Am@Nph) were prepared. The synthesized nanocomposite was characterized by (FT-IR), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), vibrating Sample Magnetometry (VSM) and Termogravimetric Analysis (TGA). The 2-hydroxy-1-naphthaldehyde modified Fe3O4@CS@Am@Nph nanocomposite was used as an effective adsorbent for removal of everzol black from aqueous solutions by batch adsorption procedure. The effects of important parameters on the surface absorption process of everzol black dye, including pH, contact time, adsorbent dosage and initial dye concentration were studied. The Langmuir, Freundlich and Temkin adsorption models were used to describe adsorption isotherms and constants. The equilibrium results revealed that the adsorption behavior of the everzol black dye on the Fe3O4@CS@Am@Nph nanocomposite fitted well with the Langmuir model. On the basis of the Langmuir analysis, the maximum adsorption capacity (qm) of the Fe3O4@CS@Am@Nph for everzol black was found to be 63.69 mg/g. The kinetic studies indicated that adsorption in all cases to be a pseudo second-order process. Further, the thermodynamic studies showed the adsorption to be a spontaneous and endothermic process.
Dim artificial light at night alters gene expression rhythms and growth in a key seagrass species (Posidonia oceanica)
Authors: Dalle Carbonare L. , Basile A. , Rindi L. , Bulleri F. , Hamedeh H. , Iacopino S. , Shukla V. , Weits D. A. , Lombardi L. , Sbrana A. , Benedetti-Cecchi L. , Giuntoli B. , Licausi F. , Maggi E. 
Published: June 2023

AbstractArtificial light at night (ALAN) is a globally spreading anthropogenic stressor, affecting more than 20% of coastal habitats. The alteration of the natural light/darkness cycle is expected to impact the physiology of organisms by acting on the complex circuits termed as circadian rhythms. Our understanding of the impact of ALAN on marine organisms is lagging behind that of terrestrial ones, and effects on marine primary producers are almost unexplored. Here, we investigated the molecular and physiological response of the Mediterranean seagrass, Posidonia oceanica (L.) Delile, as model to evaluate the effect of ALAN on seagrass populations established in shallow waters, by taking advantage of a decreasing gradient of dim nocturnal light intensity (from < 0.01 to 4 lx) along the NW Mediterranean coastline. We first monitored the fluctuations of putative circadian-clock genes over a period of 24 h along the ALAN gradient. We then investigated whether key physiological processes, known to be synchronized with day length by the circadian rhythm, were also affected by ALAN. ALAN influenced the light signalling at dusk/night in P. oceanica, including that of shorter blue wavelengths, through the ELF3–LUX1–ZTL regulatory network, and suggested that the daily perturbation of internal clock orthologs in seagrass might have caused the recruitment of PoSEND33 and PoPSBS genes to mitigate the repercussions of a nocturnal stress on photosynthesis during the day. A long-lasting impairment of gene fluctuations in sites characterised by ALAN could explain the reduced growth of the seagrass leaves when these were transferred into controlled conditions and without lighting during the night. Our results highlight the potential contribution of ALAN to the global loss of seagrass meadows, posing questions about key interactions with a variety of other human-related stressors in urban areas, in order to develop more efficient strategies to globally preserve these coastal foundation species.