bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Evaluation of the Onset and Evolution for the Non‐Darcy Behavior of the Partially Filled Rough Fracture
Authors: Zhang Shuai , Liu Xiaoli , Wang Enzhi 
Published: February 2024

AbstractThe non‐Darcy flow behavior in unfilled and fully filled rough fractures has been investigated thoroughly for decades. Natural fractures usually be partially filled with porous media due to long‐term internal and external dynamic disturbances and water flow erosion. However, how to evaluate the nonlinear seepage characteristics of the partially filled rough fracture (PFRF) is never scrutinized. In the present study, 2D direct numerical simulations are conducted to investigate the non‐Darcy behavior for flow through 6 PFRF models under different filling conditions (i.e., filling degree, roughness, and hydraulic conductivity capability of the filling medium), which included coupling between the free and seepage flow in the unfilled and filled region, respectively. The results show that the critical non‐Darcy factor E = 0.02 can be used to judge the onset of the non‐Darcy regime in PFRF, which is also the critical point of eddy region (ER) volume mutation. The higher the filling degree and the weaker the hydraulic conductivity of the filled medium, the more significant the non‐Darcy behavior. Furthermore, the variation of ER volume can be divided into three stages with the increasing inertia effect, that is, stable stage (E < 0.02), slow nonlinear growth stage (0.02 ≤ E ≤ 0.1), and rapid linear growth stage (E > 0.1). In addition, a new model for quantitatively evaluating the non‐Darcy behavior of PFRF is developed via gene expression programming based on 735 simulation data set, which is further employed to establish the relationship between the friction factor.
Cost and time-efficient construction of a 3′-end mRNA library from unpurified bulk RNA in a single tube
Authors: Choi Jungwon , Hyun Jungheun , Hyun Jieun , Kim Jae-Hee , Lee Ji Hyun , Bang Duhee 
Published: February 2024

AbstractThe major drawbacks of RNA sequencing (RNA-seq), a remarkably accurate transcriptome profiling method, is its high cost and poor scalability. Here, we report a highly scalable and cost-effective method for transcriptomics profiling called Bulk transcriptOme profiling of cell Lysate in a single poT (BOLT-seq), which is performed using unpurified bulk 3′-end mRNA in crude cell lysates. During BOLT-seq, RNA/DNA hybrids are directly subjected to tagmentation, and second-strand cDNA synthesis and RNA purification are omitted, allowing libraries to be constructed in 2 h of hands-on time. BOLT-seq was successfully used to cluster small molecule drugs based on their mechanisms of action and intended targets. BOLT-seq competes effectively with alternative library construction and transcriptome profiling methods.
The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis
Authors: Ando Yutaro , Tsukasaki Masayuki , Huynh Nam Cong-Nhat , Zang Shizao , Yan Minglu , Muro Ryunosuke , Nakamura Kazutaka , Komagamine Masatsugu , Komatsu Noriko , Okamoto Kazuo , Nakano Kenta , Okamura Tadashi , Yamaguchi Akira , Ishihara Kazuyuki , Takayanagi Hiroshi 
Published: February 2024

AbstractThe immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNA-sequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.
AF1q is a universal marker of neuroblastoma that sustains N-Myc expression and drives tumorigenesis
Authors: Oskouian Babak , Lee Joanna Y. , Asgharzadeh Shahab , Khan Ranjha , Zhang Meng , Weisbrod Julia R. , Choi Youn-Jeong , Puri Latika , Aguilar Ana E. , Zhao Piming , Saba Julie D. 
Published: February 2024

AbstractNeuroblastoma is the most common extracranial malignant tumor of childhood, accounting for 15% of all pediatric cancer deaths. Despite significant advances in our understanding of neuroblastoma biology, five-year survival rates for high-risk disease remain less than 50%, highlighting the importance of identifying novel therapeutic targets to combat the disease.MYCNamplification is the most frequent and predictive molecular aberration correlating with poor outcome in neuroblastoma. N-Myc is a short-lived protein primarily due to its rapid proteasomal degradation, a potentially exploitable vulnerability in neuroblastoma. AF1q is an oncoprotein with established roles in leukemia and solid tumor progression. It is normally expressed in brain and sympathetic neurons and has been postulated to play a part in neural differentiation. However, no role for AF1q in tumors of neural origin has been reported. In this study, we found AF1q to be a universal marker of neuroblastoma tumors. Silencing AF1q in neuroblastoma cells caused proteasomal degradation of N-Myc through Ras/ERK and AKT/GSK3β pathways, activated p53 and blocked cell cycle progression, culminating in cell death via the intrinsic apoptotic pathway. Moreover, silencing AF1q attenuated neuroblastoma tumorigenicity in vivo signifying AF1q’s importance in neuroblastoma oncogenesis. Our findings reveal AF1q to be a novel regulator of N-Myc and potential therapeutic target in neuroblastoma.
Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia
Authors: Zhou Chao , Tang Xiaowei , Yu Miao , Zhang Hongying , Zhang Xiaobin , Gao Ju , Zhang Xiangrong , Chen Jiu 
Published: February 2024

AbstractDeficit schizophrenia (DS) is a subtype of schizophrenia characterized by the primary and persistent negative symptoms. Previous studies have identified differences in brain functions between DS and non-deficit schizophrenia (NDS) patients. However, the genetic regulation features underlying these abnormal changes are still unknown. This study aimed to detect the altered patterns of functional connectivity (FC) in DS and NDS and investigate the gene expression profiles underlying these abnormal FC. The study recruited 82 DS patients, 96 NDS patients, and 124 healthy controls (CN). Voxel-based unbiased brain-wide association study was performed to reveal altered patterns of FC in DS and NDS patients. Machine learning techniques were used to access the utility of altered FC for diseases diagnosis. Weighted gene co-expression network analysis (WGCNA) was employed to explore the associations between altered FC and gene expression of 6 donated brains. Enrichment analysis was conducted to identify the genetic profiles, and the spatio-temporal expression patterns of the key genes were further explored. Comparing to CN, 23 and 20 brain regions with altered FC were identified in DS and NDS patients. The altered FC among these regions showed significant correlations with the SDS scores and exhibited high efficiency in disease classification. WGCNA revealed associations between DS/NDS-related gene expression and altered FC. Additionally, 22 overlapped genes, including 12 positive regulation genes and 10 negative regulation genes, were found between NDS and DS. Enrichment analyses demonstrated relationships between identified genes and significant pathways related to cellular response, neuro regulation, receptor binding, and channel activity. Spatial and temporal gene expression profiles of SCN1B showed the lowest expression at the initiation of embryonic development, while DPYSL3 exhibited rapid increased in the fetal. The present study revealed different altered patterns of FC in DS and NDS patients and highlighted the potential value of FC in disease classification. The associations between gene expression and neuroimaging provided insights into specific and common genetic regulation underlying these brain functional changes in DS and NDS, suggesting a potential genetic-imaging pathogenesis of schizophrenia.
Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling
Authors: Cai Zhengnan , Li Wan , Hager Sonja , Wilson Jayne Louise , Afjehi-Sadat Leila , Heiss Elke H. , Weichhart Thomas , Heffeter Petra , Weckwerth Wolfram 
Published: February 2024

AbstractPhosphoglycerate dehydrogenase (PHGDH) has emerged as a crucial factor in macromolecule synthesis, neutralizing oxidative stress, and regulating methylation reactions in cancer cells, lymphocytes, and endothelial cells. However, the role of PHGDH in tumor-associated macrophages (TAMs) is poorly understood. Here, we found that the T helper 2 (Th2) cytokine interleukin-4 and tumor-conditioned media upregulate the expression of PHGDH in macrophages and promote immunosuppressive M2 macrophage activation and proliferation. Loss of PHGDH disrupts cellular metabolism and mitochondrial respiration, which are essential for immunosuppressive macrophages. Mechanistically, PHGDH-mediated serine biosynthesis promotes α-ketoglutarate production, which activates mTORC1 signaling and contributes to the maintenance of an M2-like macrophage phenotype in the tumor microenvironment. Genetic ablation of PHGDH in macrophages from tumor-bearing mice results in attenuated tumor growth, reduced TAM infiltration, a phenotypic shift of M2-like TAMs toward an M1-like phenotype, downregulated PD-L1 expression and enhanced antitumor T-cell immunity. Our study provides a strong basis for further exploration of PHGDH as a potential target to counteract TAM-mediated immunosuppression and hinder tumor progression.
Automatic data-driven design and 3D printing of custom ocular prostheses
Authors: Reinhard Johann , Urban Philipp , Bell Stephen , Carpenter David , Sagoo Mandeep S. 
Published: February 2024

AbstractMillions of people require custom ocular prostheses due to eye loss or congenital defects. The current fully manual manufacturing processes used by highly skilled ocularists are time-consuming with varying quality. Additive manufacturing technology has the potential to simplify the manufacture of ocular prosthetics, but existing approaches just replace to various degrees craftsmanship by manual digital design and still require substantial expertise and time. Here we present an automatic digital end-to-end process for producing custom ocular prostheses that uses image data from an anterior segment optical coherence tomography device and considers both shape and appearance. Our approach uses a statistical shape model to predict, based on incomplete surface information of the eye socket, a best fitting prosthesis shape. We use a colour characterized image of the healthy fellow eye to determine and procedurally generate the prosthesis’s appearance that matches the fellow eye. The prosthesis is manufactured using a multi-material full-colour 3D printer and postprocessed to satisfy regulatory compliance. We demonstrate the effectiveness of our approach by presenting results for 10 clinic patients who received a 3D printed prosthesis. Compared to a current manual process, our approach requires five times less labour of the ocularist and produces reproducible output.
In-vivo integration of soft neural probes through high-resolution printing of liquid electronics on the cranium
Authors: Park Young-Geun , Kwon Yong Won , Koh Chin Su , Kim Enji , Lee Dong Ha , Kim Sumin , Mun Jongmin , Hong Yeon-Mi , Lee Sanghoon , Kim Ju-Young , Lee Jae-Hyun , Jung Hyun Ho , Cheon Jinwoo , Chang Jin Woo , Park Jang-Ung 
Published: February 2024

AbstractCurrent soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and restrict the free behavior of a subject. We report a soft, conformable neural interface system that can monitor the single-unit activities of neurons with long-term stability. The system implements soft neural probes in the brain, and their subsidiary electronics which are directly printed on the cranial surface. The high-resolution printing of liquid metals forms soft neural probes with a cellular-scale diameter and adaptable lengths. Also, the printing of liquid metal-based circuits and interconnections along the curvature of the cranium enables the conformal integration of electronics to the body, and the cranial circuit delivers neural signals to a smartphone wirelessly. In the in-vivo studies using mice, the system demonstrates long-term recording (33 weeks) of neural activities in arbitrary brain regions. In T-maze behavioral tests, the system shows the behavior-induced activation of neurons in multiple brain regions.
Measuring sub-nanometer undulations at microsecond temporal resolution with metal- and graphene-induced energy transfer spectroscopy
Authors: Chen Tao , Karedla Narain , Enderlein Jörg 
Published: February 2024

AbstractOut-of-plane fluctuations, also known as stochastic displacements, of biological membranes play a crucial role in regulating many essential life processes within cells and organelles. Despite the availability of various methods for quantifying membrane dynamics, accurately quantifying complex membrane systems with rapid and tiny fluctuations, such as mitochondria, remains a challenge. In this work, we present a methodology that combines metal/graphene-induced energy transfer (MIET/GIET) with fluorescence correlation spectroscopy (FCS) to quantify out-of-plane fluctuations of membranes with simultaneous spatiotemporal resolution of approximately one nanometer and one microsecond. To validate the technique and spatiotemporal resolution, we measure bending undulations of model membranes. Furthermore, we demonstrate the versatility and applicability of MIET/GIET-FCS for studying diverse membrane systems, including the widely studied fluctuating membrane system of human red blood cells, as well as two unexplored membrane systems with tiny fluctuations, a pore-spanning membrane, and mitochondrial inner/outer membranes.
Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
Authors: Bin Jenea M. , Suminaite Daumante , Benito-Kwiecinski Silvia K. , Kegel Linde , Rubio-Brotons Maria , Early Jason J. , Soong Daniel , Livesey Matthew R. , Poole Richard J. , Lyons David A. 
Published: February 2024

AbstractAxon diameter influences the conduction properties of myelinated axons, both directly, and indirectly through effects on myelin. However, we have limited understanding of mechanisms controlling axon diameter growth in the central nervous system, preventing systematic dissection of how manipulating diameter affects myelination and conduction along individual axons. Here we establish zebrafish to study axon diameter. We find that importin 13b is required for axon diameter growth, but does not affect cell body size or axon length. Using neuron-specific ipo13b mutants, we assess how reduced axon diameter affects myelination and conduction, and find no changes to myelin thickness, precision of action potential propagation, or ability to sustain high frequency firing. However, increases in conduction speed that occur along single myelinated axons with development are tightly linked to their growth in diameter. This suggests that axon diameter growth is a major driver of increases in conduction speeds along myelinated axons over time.
Light-induced switching between singlet and triplet superconducting states
Authors: Gassner Steven , Weber Clara S. , Claassen Martin 
Published: February 2024

AbstractWhile the search for topological triplet-pairing superconductivity has remained a challenge, recent developments in optically stabilizing metastable superconducting states suggest a new route to realizing this elusive phase. Here, we devise a testable theory of competing superconducting orders that permits ultrafast switching to an opposite-parity superconducting phase in centrosymmetric crystals with strong spin-orbit coupling. Using both microscopic and phenomenological models, we show that dynamical inversion symmetry breaking with a tailored light pulse can induce odd-parity (spin triplet) order parameter oscillations in a conventional even-parity (spin singlet) superconductor, which when driven strongly can send the system to a competing minimum in its free energy landscape. Our results provide new guiding principles for engineering unconventional electronic phases using light, suggesting a fundamentally non-equilibrium route toward realizing topological superconductivity.
A release of local subunit conformational heterogeneity underlies gating in a muscle nicotinic acetylcholine receptor
Authors: Thompson Mackenzie J. , Mansoub Bekarkhanechi Farid , Ananchenko Anna , Nury Hugues , Baenziger John E. 
Published: February 2024

AbstractSynaptic receptors respond to neurotransmitters by opening an ion channel across the post-synaptic membrane to elicit a cellular response. Here we use recent Torpedo acetylcholine receptor structures and functional measurements to delineate a key feature underlying allosteric communication between the agonist-binding extracellular and channel-gating transmembrane domains. Extensive mutagenesis at this inter-domain interface re-affirms a critical energetically coupled role for the principal α subunit β1-β2 and M2-M3 loops, with agonist binding re-positioning a key β1-β2 glutamate/valine to facilitate the outward motions of a conserved M2-M3 proline to open the channel gate. Notably, the analogous structures in non-α subunits adopt a locally active-like conformation in the apo state even though each L9’ hydrophobic gate residue in each pore-lining M2 α-helix is closed. Agonist binding releases local conformational heterogeneity transitioning all five subunits into a conformationally symmetric open state. A release of conformational heterogeneity provides a framework for understanding allosteric communication in pentameric ligand-gated ion channels.
Herbicide leakage into seawater impacts primary productivity and zooplankton globally
Authors: Yang Liqiang , He Xiaotong , Ru Shaoguo , Zhang Yongyu 
Published: February 2024

AbstractPredicting the magnitude of herbicide impacts on marine primary productivity remains challenging because the extent of worldwide herbicide pollution in coastal waters and the concentration-response relationships of phytoplankton communities to multiple herbicides are unclear. By analyzing the spatiotemporal distribution of herbicides at 661 bay and gulf stations worldwide from 1990 to 2022, we determined median, third quartile and maximum concentrations of 12 triazine herbicides of 0.18 nmol L−1, 1.27 nmol L−1 and 29.50 nmol L−1 (95%Confidence Interval: CI 1.06, 1.47), respectively. Under current herbicide stress, phytoplankton primary productivity was inhibited by more than 5% at 25% of the sites and by more than 10% at 10% of the sites (95%CI 3.67, 4.34), due to the inhibition of highly abundant sensitive species, community structure/particle size succession (from Bacillariophyta to Dinophyceae and from nano-phytoplankton to micro-phytoplankton), and resulting growth rate reduction. Concurrently, due to food chain cascade effects, the dominant micro-zooplankton population shifted from larger copepod larvae to smaller unicellular ciliates, which might prolong the transmission process in marine food chain and reduce the primary productivity transmission efficiency. As herbicide application rates on farmlands worldwide are correlated with residues in their adjacent seas, a continued future increase in herbicide input may seriously affect the stability of coastal waters.
Core clock genes adjust growth cessation time to day-night switches in poplar
Authors: Alique Daniel , Redondo López Arturo , González Schain Nahuel , Allona Isabel , Wabnik Krzysztof , Perales Mariano 
Published: February 2024

AbstractPoplar trees use photoperiod as a precise seasonal indicator, synchronizing plant phenology with the environment. Daylength cue determines FLOWERING LOCUS T 2 (FT2) daily expression, crucial for shoot apex development and establishment of the annual growing period. However, limited evidence exists for the molecular factors controlling FT2 transcription and the conservation with the photoperiodic control of Arabidopsis flowering. We demonstrate that FT2 expression mediates growth cessation response quantitatively, and we provide a minimal data-driven model linking core clock genes to FT2 daily levels. GIGANTEA (GI) emerges as a critical inducer of the FT2 activation window, time-bound by TIMING OF CAB EXPRESSION (TOC1) and LATE ELONGATED HYPOCOTYL (LHY2) repressions. CRISPR/Cas9 loss-of-function lines validate these roles, identifying TOC1 as a long-sought FT2 repressor. Additionally, model simulations predict that FT2 downregulation upon daylength shortening results from a progressive narrowing of this activation window, driven by the phase shift observed in the preceding clock genes. This circadian-mediated mechanism enables poplar to exploit FT2 levels as an accurate daylength-meter.
Structural models of genome-wide covariance identify multiple common dimensions in autism
Authors: de Hoyos Lucía , Barendse Maria T. , Schlag Fenja , van Donkelaar Marjolein M. J. , Verhoef Ellen , Shapland Chin Yang , Klassmann Alexander , Buitelaar Jan , Verhulst Brad , Fisher Simon E. , Rai Dheeraj , St Pourcain Beate 
Published: February 2024

AbstractCommon genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.