bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mid‐Lithospheric Discontinuity Caused by Channel Flow in Proto‐Cratonic Mantle
Authors: Yang Haibin , Artemieva Irina M. , Thybo Hans 
Published: March 2023

AbstractGlobal geophysical observations show the presence of the enigmatic mid‐lithospheric discontinuity (MLD) at depths of ca. 80–150 km which may question the stability and internal structure of the continental lithosphere. While various mechanisms may explain the MLD, the dynamic processes leading to the seismic observations are unclear. Here we present a physical mechanism for the origin of MLD by channel flow in the cratonic mantle lithosphere, triggered by convective instabilities at cratonic margins in the Archean when the mantle was hot. Our numerical modeling shows that the top of the frozen‐in channel flow creates a shear zone at a depth comparable to the globally observed seismic MLD. Grain size reduction in the shear zone and accumulation of percolated melts or fluids along the channel top may reduce seismic wave speeds as observed below the MLD, while the channel flow itself may explain radial anisotropy of seismic wave speeds and change in direction of the seismic anisotropic fast axis. The proposed mechanism is valid for a broad range of physically realistic parameters and that MLD may have been preserved since its formation in the Archean. The intensity of the channel flow ceased with time due to secular cooling of the Earth's interior. The new mechanism may reshape our understanding of the evolution and stability of cratonic lithosphere.
Iron Loss During Continental Weathering in the Early Carboniferous Period Recorded by Karst Bauxites
Authors: Ling Kunyue , Wen Hanjie , Fan Haifeng , Zhu Xiangkun , Li Zhihong , Zhang Zhengwei , Grasby Stephen E. 
Published: March 2023

AbstractSignificant iron (Fe) loss can occur during continental weathering and efflux to the ocean via runoff, historically affecting global Fe cycling and marine ecosystems. Here, we report extremely low Fe content in early Carboniferous (ca. 340 Ma) bauxites in southwestern China. These bauxites were formed by redeposition of terrestrial soils along the paleo‐continental margin of the western South China Plate in warm climates. The bauxites contain high δ56Fe (−0.17‰ to +1.15‰) values with a negative correlation between Fe2O3 and δ56Fe, indicating that a substantial amount of Fe(III) was reduced to isotopically light dissolved Fe(II) and effuxed to the ocean via reductive dissolution under anoxic conditions. The low Corg content and low FeHR/FeT, Mo/Al, U/Al, and V/Al ratios of bauxite suggest that this reduction process occurred during the pedogenic (continental weathering) rather than the depositional/diagenetic stage of karst bauxite formation. Most of the dissolved Fe(II) were rapidly re‐oxidized to Fe(III) and transported toward the paleo‐continental margin forming iron ores with δ56Fe values around zero (−0.13‰ to +0.16‰). The negative correlation between Al2O3 and Fe2O3 contents in global karst bauxites suggests common Fe loss processes during continental weathering in geological periods favoring karst bauxite formation, such as during the Carboniferous, Permian, and Cretaceous periods and the Cenozoic era. Karst bauxite may thus provide a record of Fe loss during continental weathering and act as an indicator of enhanced Fe flux to oceans.
A Robust Estimate of Continental‐Scale Terrestrial Carbon Sinks Using GOSAT XCO2 Retrievals
Authors: Zhang Lingyu , Jiang Fei , He Wei , Wu Mousong , Wang Jun , Ju Weimin , Wang Hengmao , Zhang Yongguang , Sitch Stephen , Walker Anthony P. , Yue Xu , Feng Shuzhuang , Jia Mengwei , Chen Jing M. 
Published: March 2023

AbstractSatellite XCO2 retrievals could improve the estimates of surface carbon fluxes, but it remains unknown on what scales these estimates are robust. Here, we use the time‐dependent Bayesian synthesis top‐down method and prior net ecosystem exchanges (NEEs) from 12 terrestrial biosphere models (TBMs) to infer the monthly carbon fluxes of 51 land regions with constraints by GOSAT XCO2 retrievals. We find that the uncertainty (standard deviation of 12 TBMs) reduction rates (uncertainty reduction rate (URR)) decrease significantly at decreasing spatial scales. On the continental‐scale, the mean URR is about 57%, and the annual and seasonal cycle estimates of NEE are rather robust. The evaluation shows that the posterior CO2 concentrations are significantly improved at the continental scale. Our study suggests that the GOSAT XCO2 can only promise a robust continental‐scale NEE estimate, and improving the XCO2 accuracy is an effective way to achieve robust estimates on smaller scales under current spatial coverage.
Cooperative antibiotic resistance facilitates horizontal gene transfer
Authors: Wang Qinqin , Wei Shaodong , Silva Ana Filipa , Madsen Jonas Stenløkke 
Published: March 2023

Abstract
The rise of β-lactam resistance among pathogenic bacteria, due to the horizontal transfer of plasmid-encoded β-lactamases, is a current global health crisis. Importantly, β-lactam hydrolyzation by β-lactamases, not only protects the producing cells but also sensitive neighboring cells cooperatively. Yet, how such cooperative traits affect plasmid transmission and maintenance is currently poorly understood. Here we experimentally show that KPC-2 β-lactamase expression and extracellular activity were higher when encoded on plasmids compared with the chromosome, resulting in the elevated rescue of sensitive non-producers. This facilitated efficient plasmid transfer to the rescued non-producers and expanded the potential plasmid recipient pool and the probability of plasmid transfer to new genotypes. Social conversion of non-producers by conjugation was efficient yet not absolute. Non-cooperative plasmids, not encoding KPC-2, were moderately more competitive than cooperative plasmids when β-lactam antibiotics were absent. However, in the presence of a β-lactam antibiotic, strains with non-cooperative plasmids were efficiently outcompeted. Moreover, plasmid-free non-producers were more competitive than non-producers imposed with the metabolic burden of a plasmid. Our results suggest that cooperative antibiotic resistance especially promotes the fitness of replicons that transfer horizontally such as conjugative plasmids.
The impact of childhood glaucoma on psychosocial functioning and quality of life: a review of the literature
Authors: McLaughlin Danielle E. , Semrov Ana , Munshi Hounsh , Patel Annika J. , Rahi Jugnoo , Grajewski Alana L. ,   Balkan CGRN Study Group, Bitrian Elena , Brandt James D. , Chang Ta Chen , Dada Tanuj , Delamater Alan , Edmunds Beth , Freedman Sharon F. , Hodapp Elizabeth , Kim Youngmee 
Published: March 2023

AbstractWe present a novel comprehensive literature review of studies of the psychosocial functioning (PF) and quality of life (QoL) of patients with childhood glaucoma and their caregivers. Our findings demonstrate variable study quality and approach, as well as inconsistent results relating to the association of glaucoma-specific factors and sociodemographic variables with measured PF and QoL. Future studies should focus on the development of culturally cognizant and standardized assessment tools, execution of multi-center longitudinal studies with global representation, evaluation of PF and QoL among siblings and childhood glaucoma providers, and implementation of interventions to improve patient and caregiver PF and QoL.
Epigenetic state determines the in vivo efficacy of STING agonist therapy
Authors: Falahat Rana , Berglund Anders , Perez-Villarroel Patricio , Putney Ryan M. , Hamaidi Imene , Kim Sungjune , Pilon-Thomas Shari , Barber Glen N. , Mulé James J. 
Published: March 2023

AbstractWhile STING-activating agents have shown limited efficacy in early-phase clinical trials, multiple lines of evidence suggest the importance of tumor cell-intrinsic STING function in mediating antitumor immune responses. Although STING signaling is impaired in human melanoma, its restoration through epigenetic reprogramming can augment its antigenicity and T cell recognition. In this study, we show that reversal of methylation silencing of STING in murine melanoma cell lines using a clinically available DNA methylation inhibitor can improve agonist-induced STING activation and type-I IFN induction, which, in tumor-bearing mice, can induce tumor regression through a CD8+ T cell-dependent immune response. These findings not only provide mechanistic insight into how STING signaling dysfunction in tumor cells can contribute to impaired responses to STING agonist therapy, but also suggest that pharmacological restoration of STING signaling through epigenetic reprogramming might improve the therapeutic efficacy of STING agonists.
Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease
Authors: Lia Annamaria , Sansevero Gabriele , Chiavegato Angela , Sbrissa Miriana , Pendin Diana , Mariotti Letizia , Pozzan Tullio , Berardi Nicoletta , Carmignoto Giorgio , Fasolato Cristina , Zonta Micaela 
Published: March 2023

AbstractCalcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present a longitudinal study in the PS2APP mouse model of Alzheimer’s disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At the onset of plaque deposition, somatosensory cortical astrocytes of AD female mice exhibit a drastic reduction of Ca2+ signaling, closely associated with decreased endoplasmic reticulum Ca2+ concentration and reduced expression of the Ca2+ sensor STIM1. In parallel, astrocyte-dependent long-term synaptic plasticity declines in the somatosensory circuitry, anticipating specific tactile memory loss. Notably, we show that both astrocyte Ca2+ signaling and long-term synaptic plasticity are fully recovered by selective STIM1 overexpression in astrocytes. Our data unveil astrocyte Ca2+ hypoactivity in neocortical astrocytes as a functional hallmark of early AD stages and indicate astrocytic STIM1 as a target to rescue memory deficits.
Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer
Authors: Cotto Kelsy C. , Feng Yang-Yang , Ramu Avinash , Richters Megan , Freshour Sharon L. , Skidmore Zachary L. , Xia Huiming , McMichael Joshua F. , Kunisaki Jason , Campbell Katie M. , Chen Timothy Hung-Po , Rozycki Emily B. , Adkins Douglas , Devarakonda Siddhartha , Sankararaman Sumithra , Lin Yiing , Chapman William C. , Maher Christopher A. , Arora Vivek , Dunn Gavin P. , Uppaluri Ravindra , Govindan Ramaswamy , Griffith Obi L. , Griffith Malachi 
Published: March 2023

AbstractSomatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools (www.regtools.org), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique junctions. To characterize these somatic variants and their associated splice isoforms, we annotate them with the Variant Effect Predictor, SpliceAI, and Genotype-Tissue Expression junction counts and compare our results to other tools that integrate genomic and transcriptomic data. While many events are corroborated by the aforementioned tools, the flexibility of RegTools also allows us to identify splice-associated variants in known cancer drivers, such asTP53,CDKN2A, andB2M, and other genes.
IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis
Authors: Lin Weiwei , Niu Rui , Park Seong-Min , Zou Yan , Kim Sung Soo , Xia Xue , Xing Songge , Yang Qingshan , Sun Xinhong , Yuan Zheng , Zhou Shuchang , Zhang Dongya , Kwon Hyung Joon , Park Saewhan , Il Kim Chan , Koo Harim , Liu Yang , Wu Haigang , Zheng Meng , Yoo Heon , Shi Bingyang , Park Jong Bae , Yin Jinlong 
Published: March 2023

AbstractDiffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.
A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth
Authors: Wang Chong , Liu Xiang , Liang Jun , Narita Yohei , Ding Weiyue , Li Difei , Zhang Luyao , Wang Hongbo , Leong Merrin Man Long , Hou Isabella , Gerdt Catherine , Jiang Chang , Zhong Qian , Tang Zhonghui , Forney Carmy , Kottyan Leah , Weirauch Matthew T. , Gewurz Benjamin E. , Zeng Mu-sheng , Jiang Sizun , Teng Mingxiang , Zhao Bo 
Published: March 2023

AbstractEpstein-Barr virus (EBV) immortalization of resting B lymphocytes (RBLs) to lymphoblastoid cell lines (LCLs) models human DNA tumor virus oncogenesis. RBL and LCL chromatin interaction maps are compared to identify the spatial and temporal genome architectural changes during EBV B cell transformation. EBV induces global genome reorganization where contact domains frequently merge or subdivide during transformation. Repressed B compartments in RBLs frequently switch to active A compartments in LCLs. LCLs gain 40% new contact domain boundaries. Newly gained LCL boundaries have strong CTCF binding at their borders while in RBLs, the same sites have much less CTCF binding. Some LCL CTCF sites also have EBV nuclear antigen (EBNA) leader protein EBNALP binding. LCLs have more local interactions than RBLs at LCL dependency factors and super-enhancer targets. RNA Pol II HiChIP and FISH of RBL and LCL further validate the Hi-C results. EBNA3A inactivation globally alters LCL genome interactions. EBNA3A inactivation reduces CTCF and RAD21 DNA binding. EBNA3C inactivation rewires the looping at the CDKN2A/B and AICDA loci. Disruption of a CTCF site at AICDA locus increases AICDA expression. These data suggest that EBV controls lymphocyte growth by globally reorganizing host genome architecture to facilitate the expression of key oncogenes.
RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
Authors: Jbara Amina , Lin Kuan-Ting , Stossel Chani , Siegfried Zahava , Shqerat Haya , Amar-Schwartz Adi , Elyada Ela , Mogilevsky Maxim , Raitses-Gurevich Maria , Johnson Jared L. , Yaron Tomer M. , Ovadia Ofek , Jang Gun Ho , Danan-Gotthold Miri , Cantley Lewis C. , Levanon Erez Y. , Gallinger Steven , Krainer Adrian R. , Golan Talia , Karni Rotem 
Published: March 2023

AbstractPancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation is correlated with the dissemination of metastases1–3. Here we analysed RNA splicing data of a large cohort of primary and metastatic PDA tumours to identify differentially spliced events that correlate with PDA progression. De novo motif analysis of these events detected enrichment of motifs with high similarity to the RBFOX2 motif. Overexpression of RBFOX2 in a patient-derived xenograft (PDX) metastatic PDA cell line drastically reduced the metastatic potential of these cells in vitro and in vivo, whereas depletion of RBFOX2 in primary pancreatic tumour cell lines increased the metastatic potential of these cells. These findings support the role of RBFOX2 as a potent metastatic suppressor in PDA. RNA-sequencing and splicing analysis of RBFOX2 target genes revealed enrichment of genes in the RHO GTPase pathways, suggesting a role of RBFOX2 splicing activity in cytoskeletal organization and focal adhesion formation. Modulation of RBFOX2-regulated splicing events, such as via myosin phosphatase RHO-interacting protein (MPRIP), is associated with PDA metastases, altered cytoskeletal organization and the induction of focal adhesion formation. Our results implicate the splicing-regulatory function of RBFOX2 as a tumour suppressor in PDA and suggest a therapeutic approach for metastatic PDA.
Genome assembly of the ectoparasitoid wasp Theocolax elegans
Authors: Xiao Shan , Ye Xinhai , Wang Shuping , Yang Yi , Fang Qi , Wang Fang , Ye Gongyin 
Published: March 2023

AbstractThe ectoparasitoid waspTheocolax elegansis a cosmopolitan and generalist pteromalid parasitoid of several major storage insect pests, and can effectively suppress a host population in warehouses. However, little molecular information about this wasp is currently available. In this study, we assembled the genome ofT. elegansusing PacBio long-read sequencing, Illumina sequencing, and Hi-C methods. The genome assembly is 662.73 Mb in length with contig and scaffold N50 values of 1.15 Mb and 88.8 Mb, respectively. The genome contains 56.4% repeat sequences and 23,212 protein-coding genes were annotated. Phylogenomic analyses revealed thatT. elegansdiverged from the lineage leading to subfamily Pteromalinae (Nasonia vitripennisandPteromalus puparum) approximately 110.5 million years ago. We identified 130 significantly expanded gene families, 34 contracted families, 248 fast-evolving genes, and 365 positively selected genes inT. elegans. Additionally, 260 olfactory receptors and 285 venom proteins were identified. This genome assembly provides valuable genetic bases for future investigations on evolution, molecular biology and application ofT. elegans.
CACNA1D overexpression and voltage-gated calcium channels in prostate cancer during androgen deprivation
Authors: McKerr Niamh , Mohd-Sarip Adone , Dorrian Hannah , Breen Conor , A. James Jacqueline , McQuaid Stephen , Mills Ian G. , McCloskey Karen D. 
Published: March 2023

AbstractProstate cancer is often treated by perturbing androgen receptor signalling. CACNA1D, encoding CaV1.3 ion channels is upregulated in prostate cancer. Here we show how hormone therapy affects CACNA1D expression and CaV1.3 function. Human prostate cells (LNCaP, VCaP, C4-2B, normal RWPE-1) and a tissue microarray were used. Cells were treated with anti-androgen drug, Enzalutamide (ENZ) or androgen-removal from media, mimicking androgen-deprivation therapy (ADT). Proliferation assays, qPCR, Western blot, immunofluorescence, Ca2+-imaging and patch-clamp electrophysiology were performed. Nifedipine, Bay K 8644 (CaV1.3 inhibitor, activator), mibefradil, Ni2+ (CaV3.2 inhibitors) and high K+ depolarising solution were employed. CACNA1D and CaV1.3 protein are overexpressed in prostate tumours and CACNA1D was overexpressed in androgen-sensitive prostate cancer cells. In LNCaP, ADT or ENZ increased CACNA1D time-dependently whereas total protein showed little change. Untreated LNCaP were unresponsive to depolarising high K+/Bay K (to activate CaV1.3); moreover, currents were rarely detected. ADT or ENZ-treated LNCaP exhibited nifedipine-sensitive Ca2+-transients; ADT-treated LNCaP exhibited mibefradil-sensitive or, occasionally, nifedipine-sensitive inward currents. CACNA1D knockdown reduced the subpopulation of treated-LNCaP with CaV1.3 activity. VCaP displayed nifedipine-sensitive high K+/Bay K transients (responding subpopulation was increased by ENZ), and Ni2+-sensitive currents. Hormone therapy enables depolarization/Bay K-evoked Ca2+-transients and detection of CaV1.3 and CaV3.2 currents. Physiological and genomic CACNA1D/CaV1.3 mechanisms are likely active during hormone therapy—their modulation may offer therapeutic advantage.
Fascicle dynamics of the tibialis anterior muscle reflect whole-body walking economy
Authors: Kwak Samuel T. , Chang Young-Hui 
Published: March 2023

AbstractHumans can inherently adapt their gait pattern in a way that minimizes the metabolic cost of transport, or walking economy, within a few steps, which is faster than any known direct physiological sensor of metabolic energy. Instead, walking economy may be indirectly sensed through mechanoreceptors that correlate with the metabolic cost per step to make such gait adaptations. We tested whether velocity feedback from tibialis anterior (TA) muscle fascicles during the early stance phase of walking could potentially act to indirectly sense walking economy. As participants walked within a range of steady-state speeds and step frequencies, we observed that TA fascicles lengthen on almost every step. Moreover, the average peak fascicle velocity experienced during lengthening reflected the metabolic cost of transport of the given walking condition. We observed that the peak TA muscle activation occurred earlier than could be explained by a short latency reflex response. The activation of the TA muscle just prior to heel strike may serve as a prediction of the magnitude of the ground collision and the associated energy exchange. In this scenario, any unexpected length change experienced by the TA fascicle would serve as an error signal to the nervous system and provide additional information about energy lost per step. Our work helps provide a biomechanical framework to understand the possible neural mechanisms underlying the rapid optimization of walking economy.