bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paleo‐Evolution of Martian Subsurface Ice and Its Role in the Polar Physical and Isotopic Layering
Authors: Vos E. , Aharonson O. , Schörghofer N. , Forget F. , Lange L. , Millour E. 
Published: October 2023

AbstractMars harbors ice deposits in several forms, on the surface and in the subsurface, which exchange with each other on various timescales. We seek to study the pore ice evolution over millennial time scales and how it contributes to and affects the Polar cap's evolution. We calculate the evolution of SubSurface Ice (SSI) pore filling by coupling two models, the Mars LMD Global Climate Model, which calculates the atmospheric and surface evolution on an annual timescale, and the dynamical version of the Mars Subsurface Ice Model, which calculates the evolution of the SSI on a millennial timescale. The SSI latitudinal boundary fluctuates over more than 25° in one obliquity cycle, overall extending equatorward of latitude ±35° at high obliquity, and receding to about ±60° at low obliquity. In locations where the SSI is stable continuously over orbital cycles, the simulations predict layering caused by a sublimation front at the SSI top boundary. Between 5 and 2.5 Myr ago, the subsurface lost at least ∼95 m of polar equivalent layer ice. The SSI flux routinely reaches ∼1 mm/Mars year. In addition to the direct contribution to the growth of the North Polar Layered Deposits (NPLD), the SSI causes variations in the NPLD accumulation rate due to the changes in the SSI distribution that affect the seasonal energy budget. These variations are comparable to the change in rate due to variations in orbital elements. When running paleo‐climate simulations, particularly to reconstruct the NPLD profile, changes in the SSI distribution should be considered.
Targeting E3 ubiquitin ligases and their adaptors as a therapeutic strategy for metabolic diseases
Authors: Jeong Yelin , Oh Ah-Reum , Jung Young Hoon , Gi HyunJoon , Kim Young Un , Kim KyeongJin 
Published: October 2023

AbstractPosttranslational modification of proteins via ubiquitination determines their activation, translocation, dysregulation, or degradation. This process targets a large number of cellular proteins, affecting all biological pathways involved in the cell cycle, development, growth, and differentiation. Thus, aberrant regulation of ubiquitination is likely associated with several diseases, including various types of metabolic diseases. Among the ubiquitin enzymes, E3 ubiquitin ligases are regarded as the most influential ubiquitin enzymes due to their ability to selectively bind and recruit target substrates for ubiquitination. Continued research on the regulatory mechanisms of E3 ligases and their adaptors in metabolic diseases will further stimulate the discovery of new targets and accelerate the development of therapeutic options for metabolic diseases. In this review, based on recent discoveries, we summarize new insights into the roles of E3 ubiquitin ligases and their adaptors in the pathogenesis of metabolic diseases by highlighting recent evidence obtained in both human and animal model studies.
Spatial transcriptomics in neuroscience
Authors: Jung Namyoung , Kim Tae-Kyung 
Published: October 2023

AbstractThe brain is one of the most complex living tissue types and is composed of an exceptional diversity of cell types displaying unique functional connectivity. Single-cell RNA sequencing (scRNA-seq) can be used to efficiently map the molecular identities of the various cell types in the brain by providing the transcriptomic profiles of individual cells isolated from the tissue. However, the lack of spatial context in scRNA-seq prevents a comprehensive understanding of how different configurations of cell types give rise to specific functions in individual brain regions and how each distinct cell is connected to form a functional unit. To understand how the various cell types contribute to specific brain functions, it is crucial to correlate the identities of individual cells obtained through scRNA-seq with their spatial information in intact tissue. Spatial transcriptomics (ST) can resolve the complex spatial organization of cell types in the brain and their connectivity. Various ST tools developed during the past decade based on imaging and sequencing technology have permitted the creation of functional atlases of the brain and have pulled the properties of neural circuits into ever-sharper focus. In this review, we present a summary of several ST tools and their applications in neuroscience and discuss the unprecedented insights these tools have made possible.
Lactate as a major epigenetic carbon source for histone acetylation via nuclear LDH metabolism
Authors: An Yong Jin , Jo Sihyang , Kim Jin-Mo , Kim Han Sun , Kim Hyun Young , Jeon Sang-Min , Han Dawool , Yook Jong In , Kang Keon Wook , Park Sunghyouk 
Published: October 2023

AbstractHistone acetylation involves the transfer of two-carbon units to the nucleus that are embedded in low-concentration metabolites. We found that lactate, a high-concentration metabolic byproduct, can be a major carbon source for histone acetylation through oxidation-dependent metabolism. Both in cells and in purified nuclei, 13C3-lactate carbons are incorporated into histone H4 (maximum incorporation: ~60%). In the purified nucleus, this process depends on nucleus-localized lactate dehydrogenase (LDHA), knockout (KO) of which abrogates incorporation. Heterologous expression of nucleus-localized LDHA reverses the KO effect. Lactate itself increases histone acetylation, whereas inhibition of LDHA reduces acetylation. In vitro and in vivo settings exhibit different lactate incorporation patterns, suggesting an influence on the microenvironment. Higher nuclear LDHA localization is observed in pancreatic cancer than in normal tissues, showing disease relevance. Overall, lactate and nuclear LDHA can be major structural and regulatory players in the metabolism–epigenetics axis controlled by the cell’s own status or the environmental status.
Lipocalin-2: a therapeutic target to overcome neurodegenerative diseases by regulating reactive astrogliosis
Authors: Jung Byung-Kwon , Ryu Kwon-Yul 
Published: October 2023

AbstractGlial cell activation precedes neuronal cell death during brain aging and the progression of neurodegenerative diseases. Under neuroinflammatory stress conditions, lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin or 24p3, is produced and secreted by activated microglia and reactive astrocytes. Lcn2 expression levels are known to be increased in various cells, including reactive astrocytes, through the activation of the NF-κB signaling pathway. In the central nervous system, as LCN2 exerts neurotoxicity when secreted from reactive astrocytes, many researchers have attempted to identify various strategies to inhibit LCN2 production, secretion, and function to minimize neuroinflammation and neuronal cell death. These strategies include regulation at the transcriptional, posttranscriptional, and posttranslational levels, as well as blocking its functions using neutralizing antibodies or antagonists of its receptor. The suppression of NF-κB signaling is a strategy to inhibit LCN2 production, but it may also affect other cellular activities, raising questions about its effectiveness and feasibility. Recently, LCN2 was found to be a target of the autophagy‒lysosome pathway. Therefore, autophagy activation may be a promising therapeutic strategy to reduce the levels of secreted LCN2 and overcome neurodegenerative diseases. In this review, we focused on research progress on astrocyte-derived LCN2 in the central nervous system.
NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections
Authors: Klabunde Björn , Wesener André , Bertrams Wilhelm , Beinborn Isabell , Paczia Nicole , Surmann Kristin , Blankenburg Sascha , Wilhelm Jochen , Serrania Javier , Knoops Kèvin , Elsayed Eslam M. , Laakmann Katrin , Jung Anna Lena , Kirschbaum Andreas , Hammerschmidt Sven , Alshaar Belal , Gisch Nicolas , Abu Mraheil Mobarak , Becker Anke , Völker Uwe , Vollmeister Evelyn , Benedikter Birke J. , Schmeck Bernd 
Published: October 2023

AbstractLower respiratory tract infections caused byStreptococcus pneumoniae(Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response toSpninfection on a transcriptomic, proteomic and metabolic level. We found the NAD+salvage pathway to be dysregulated upon infection in a cell line model, primary human lung tissue and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+treatment ofSpninhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+production increased NAD+levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+treatment ofSpndysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+. Thus, we identified the NAD+salvage pathway as an antibacterial pathway inSpninfections, predicting an antibacterial mechanism of NAD+.
Global organic and inorganic aerosol hygroscopicity and its effect on radiative forcing
Authors: Pöhlker Mira L. , Pöhlker Christopher , Quaas Johannes , Mülmenstädt Johannes , Pozzer Andrea , Andreae Meinrat O. , Artaxo Paulo , Block Karoline , Coe Hugh , Ervens Barbara , Gallimore Peter , Gaston Cassandra J. , Gunthe Sachin S. , Henning Silvia , Herrmann Hartmut , Krüger Ovid O. , McFiggans Gordon , Poulain Laurent , Raj Subha S. , Reyes-Villegas Ernesto , Royer Haley M. , Walter David , Wang Yuan , Pöschl Ulrich 
Published: October 2023

AbstractThe climate effects of atmospheric aerosol particles serving as cloud condensation nuclei (CCN) depend on chemical composition and hygroscopicity, which are highly variable on spatial and temporal scales. Here we present global CCN measurements, covering diverse environments from pristine to highly polluted conditions. We show that the effective aerosol hygroscopicity,κ, can be derived accurately from the fine aerosol mass fractions of organic particulate matter (ϵorg) and inorganic ions (ϵinorg) through a linear combination,κ = ϵorg ⋅ κorg + ϵinorg ⋅ κinorg. In spite of the chemical complexity of organic matter, its hygroscopicity is well captured and represented by a global average value ofκorg = 0.12 ± 0.02 withκinorg = 0.63 ± 0.01 as the corresponding value for inorganic ions. By showing that the sensitivity of global climate forcing to changes inκorgandκinorgis small, we constrain a critically important aspect of global climate modelling.
Mechanically induced pyroptosis enhances cardiosphere oxidative stress resistance and metabolism for myocardial infarction therapy
Authors: Wang Yingwei , Li Qi , Zhao Jupeng , Chen Jiamin , Wu Dongxue , Zheng Youling , Wu Jiaxin , Liu Jie , Lu Jianlong , Zhang Jianhua , Wu Zheng 
Published: October 2023

AbstractCurrent approaches in myocardial infarction treatment are limited by low cellular oxidative stress resistance, reducing the long-term survival of therapeutic cells. Here we develop a liquid-crystal substrate with unique surface properties and mechanical responsiveness to produce size-controllable cardiospheres that undergo pyroptosis to improve cellular bioactivities and resistance to oxidative stress. We perform RNA sequencing and study cell metabolism to reveal increased metabolic levels and improved mitochondrial function in the preconditioned cardiospheres. We test therapeutic outcomes in a rat model of myocardial infarction to show that cardiospheres improve long-term cardiac function, promote angiogenesis and reduce cardiac remodeling during the 3-month observation. Overall, this study presents a promising and effective system for preparing a large quantity of functional cardiospheres, showcasing potential for clinical application.
Efficient magnetic switching in a correlated spin glass
Authors: Krempaský Juraj , Springholz Gunther , D’Souza Sunil Wilfred , Caha Ondřej , Gmitra Martin , Ney Andreas , Vaz C. A. F. , Piamonteze Cinthia , Fanciulli Mauro , Kriegner Dominik , Krieger Jonas A. , Prokscha Thomas , Salman Zaher , Minár Jan , Dil J. Hugo 
Published: October 2023

AbstractThe interplay between spin-orbit interaction and magnetic order is one of the most active research fields in condensed matter physics and drives the search for materials with novel, and tunable, magnetic and spin properties. Here we report on a variety of unique and unexpected observations in thin multiferroic Ge1−xMnxTe films. The ferrimagnetic order parameter in this ferroelectric semiconductor is found to switch direction under magnetostochastic resonance with current pulses many orders of magnitude lower as for typical spin-orbit torque systems. Upon a switching event, the magnetic order spreads coherently and collectively over macroscopic distances through a correlated spin-glass state. Utilizing these observations, we apply a novel methodology to controllably harness this stochastic magnetization dynamics.
A cleaner snow future mitigates Northern Hemisphere snowpack loss from warming
Authors: Hao Dalei , Bisht Gautam , Wang Hailong , Xu Donghui , Huang Huilin , Qian Yun , Leung L. Ruby 
Published: October 2023

AbstractLight-absorbing particles (LAP) deposited on seasonal snowpack can result in snow darkening, earlier snowmelt, and regional climate change. However, their future evolution and contributions to snowpack change relative to global warming remain unclear. Here, using Earth System Model simulations, we project significantly reduced black carbon deposition by 2081-2100, which reduces the December-May average LAP-induced radiative forcing in snow over the Northern Hemisphere from 1.3 Wm−2 during 1995-2014 to 0.65 (SSP126) and 0.49 (SSP585) Wm−2. We quantify separately the contributions of climate change and LAP evolution on future snowpack and demonstrate that projected LAP changes in snow over the Tibetan Plateau will alleviate future snowpack loss due to climate change by 52.1 ± 8.0% and 8.0 ± 1.1% at the end of the century for the two scenarios, mainly due to reduced black carbon contamination. Our findings highlight a cleaner snow future and its benefits for future water supply from snowmelt especially under the sustainable development pathway of SSP126.
Thin lamellar films with enhanced mechanical properties for durable radiative cooling
Authors: Xiong Lianhu , Wei Yun , Chen Chuanliang , Chen Xin , Fu Qiang , Deng Hua 
Published: October 2023

AbstractPassive daytime radiative cooling is a promising path to tackle energy, environment and security issues originated from global warming. However, the contradiction between desired high solar reflectivity and necessary applicable performance is a major limitation at this stage. Herein, we demonstrate a “Solvent exchange-Reprotonation” processing strategy to fabricate a lamellar structure integrating aramid nanofibers with core-shell TiO2-coated Mica microplatelets for enhanced strength and durability without compromising optical performance. Such approach enables a slow but complete two-step protonation transition and the formation of three-dimensional dendritic networks with strong fibrillar joints, where overloaded scatterers are stably grasped and anchored in alignment, thereby resulting in a high strength of ~112 MPa as well as excellent environmental durability including ultraviolet aging, high temperature, scratches, etc. Notably, the strong backward scattering excited by multiple core-shell and shell-air interfaces guarantees a balanced reflectivity (~92%) and thickness (~25 μm), which is further revealed by outdoor tests where attainable subambient temperature drops are ~3.35 °C for daytime and ~6.11 °C for nighttime. Consequently, both the cooling capacity and comprehensive outdoor-services performance, greatly push radiative cooling towards real-world applications.
Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15
Authors: Moro Ramona N. , Biswas Uddipta , Kharat Suhas S. , Duzanic Filip D. , Das Prosun , Stavrou Maria , Raso Maria C. , Freire Raimundo , Chaudhuri Arnab Ray , Sharan Shyam K. , Penengo Lorenza 
Published: October 2023

AbstractDNA replication and repair defects or genotoxic treatments trigger interferon (IFN)-mediated inflammatory responses. However, whether and how IFN signaling in turn impacts the DNA replication process has remained elusive. Here we show that basal levels of the IFN-stimulated gene 15, ISG15, and its conjugation (ISGylation) are essential to protect nascent DNA from degradation. Moreover, IFNβ treatment restores replication fork stability in BRCA1/2-deficient cells, which strictly depends on topoisomerase-1, and rescues lethality of BRCA2-deficient mouse embryonic stem cells. Although IFNβ activates hundreds of genes, these effects are specifically mediated by ISG15 and ISGylation, as their inactivation suppresses the impact of IFNβ on DNA replication. ISG15 depletion significantly reduces cell proliferation rates in human BRCA1-mutated triple-negative, whereas its upregulation results in increased resistance to the chemotherapeutic drug cisplatin in mouse BRCA2-deficient breast cancer cells, respectively. Accordingly, cells carrying BRCA1/2 defects consistently show increased ISG15 levels, which we propose as an in-built mechanism of drug resistance linked to BRCAness.
Orientation distributions of vacuum-deposited organic emitters revealed by single-molecule microscopy
Authors: Tenopala-Carmona Francisco , Hertel Dirk , Hillebrandt Sabina , Mischok Andreas , Graf Arko , Weitkamp Philipp , Meerholz Klaus , Gather Malte C. 
Published: October 2023

AbstractThe orientation of luminescent molecules in organic light-emitting diodes strongly influences device performance. However, our understanding of the factors controlling emitter orientation is limited as current measurements only provide ensemble-averaged orientation values. Here, we use single-molecule imaging to measure the transition dipole orientation of individual emitter molecules in a state-of-the-art thermally evaporated host and thereby obtain complete orientation distributions of the hyperfluorescence-terminal emitter C545T. We achieve this by realizing ultra-low doping concentrations (10−6 wt%) of C545T and minimising background levels to reliably measure its photoluminescence. This approach yields the orientation distributions of >1000 individual emitter molecules in a system relevant to vacuum-processed devices. Analysis of solution- and vacuum-processed systems reveals that the orientation distributions strongly depend on the nanoscale environment of the emitter. This work opens the door to attaining unprecedented information on the factors that determine emitter orientation in current and future material systems for organic light-emitting devices.
Multifaceted analysis of cross-tissue transcriptomes reveals phenotype–endotype associations in atopic dermatitis
Authors: Sekita Aiko , Kawasaki Hiroshi , Fukushima-Nomura Ayano , Yashiro Kiyoshi , Tanese Keiji , Toshima Susumu , Ashizaki Koichi , Miyai Tomohiro , Yazaki Junshi , Kobayashi Atsuo , Namba Shinichi , Naito Tatsuhiko , Wang Qingbo S. , Kawakami Eiryo , Seita Jun , Ohara Osamu , Sakurada Kazuhiro , Okada Yukinori , Amagai Masayuki , Koseki Haruhiko 
Published: October 2023

AbstractAtopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures. We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases.
Mechanistic insight on water dissociation on pristine low-index TiO2 surfaces from machine learning molecular dynamics simulations
Authors: Zeng Zezhu , Wodaczek Felix , Liu Keyang , Stein Frederick , Hutter Jürg , Chen Ji , Cheng Bingqing 
Published: October 2023

AbstractWater adsorption and dissociation processes on pristine low-index TiO2 interfaces are important but poorly understood outside the well-studied anatase (101) and rutile (110). To understand these, we construct three sets of machine learning potentials that are simultaneously applicable to various TiO2 surfaces, based on three density-functional-theory approximations. Here we show the water dissociation free energies on seven pristine TiO2 surfaces, and predict that anatase (100), anatase (110), rutile (001), and rutile (011) favor water dissociation, anatase (101) and rutile (100) have mostly molecular adsorption, while the simulations of rutile (110) sensitively depend on the slab thickness and molecular adsorption is preferred with thick slabs. Moreover, using an automated algorithm, we reveal that these surfaces follow different types of atomistic mechanisms for proton transfer and water dissociation: one-step, two-step, or both. These mechanisms can be rationalized based on the arrangements of water molecules on the different surfaces. Our finding thus demonstrates that the different pristine TiO2 surfaces react with water in distinct ways, and cannot be represented using just the low-energy anatase (101) and rutile (110) surfaces.
PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease
Authors: Huang Xiaobing , Wang Changliang , Zhang Tianjiao , Li Rongzhen , Chen Liang , Leung Ka Lai , Lakso Merja , Zhou Qinghua , Zhang Hongjie , Wong Garry 
Published: October 2023

AbstractPIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.