bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RNA m6A reader IGF2BP3 regulates NFAT1/IRF1 axis-mediated anti-tumor activity in gastric cancer
Authors: Ge Lichen , Rui Yalan , Wang Cheng , Wu Yingmin , Wang Hongsheng , Wang Junjun 
Published: March 2024

AbstractN6-methyladenosine (m6A) and its associated reader protein insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) are involved in tumor initiation and progression via regulating RNA metabolism. This study aims to investigate the biological function and clinical significance of IGF2BP3 in gastric cancer (GC). The clinical significance of IGF2BP3 was evaluated using tumor related databases and clinical tissues. The biological role and molecular mechanism of IGF2BP3 in GC progression were investigated by multi-omics analysis including Ribosome sequence (Ribo-seq), RNA sequence (RNA-seq) and m6A sequence (m6A-seq) combined with gain- and loss- of function experiments. IGF2BP3 expression is significantly elevated in GC tissues and associated with poor prognosis of GC patients. Knockdown of IGF2BP3 significantly weakens the migration and clonogenic ability, promotes the apoptosis, inhibits translation, and suppresses in vitro growth and progression of GC cells. Mechanistically, IGF2BP3 regulates the mRNA stability and translation of the nuclear factor of activated T cells 1(NFAT1) in a m6A dependent manner. Then NFAT1 induced by IGF2BP3 acts as a transcription factor (TF) to negatively regulates the promoter activities of interferon regulatory factor 1 (IRF1) to inhibit its expression. Inhibition of IGF2BP3-induced expression of IRF1 activates interferon (IFN) signaling pathway and then exerts its anti-tumor effect. Elevated IGF2BP3 promotes in vivo and in vitro GC progression via regulation of NFAT1/IRF1 pathways. Targeted inhibition of IGF2BP3 might be a potential therapeutic approach for GC treatment.
Cryo-EM structures reveal how phosphate release from Arp3 weakens actin filament branches formed by Arp2/3 complex
Authors: Chavali Sai Shashank , Chou Steven Z. , Cao Wenxiang , Pollard Thomas D. , De La Cruz Enrique M. , Sindelar Charles V. 
Published: March 2024

AbstractArp2/3 complex nucleates branched actin filaments for cell and organelle movements. Here we report a 2.7 Å resolution cryo-EM structure of the mature branch junction formed by S. pombe Arp2/3 complex that provides details about interactions with both mother and daughter filaments. We determine a second structure at 3.2 Å resolution with the phosphate analog BeFx bound with ADP to Arp3 and ATP bound to Arp2. In this ADP-BeFx transition state the outer domain of Arp3 is rotated 2° toward the mother filament compared with the ADP state and makes slightly broader contacts with actin in both the mother and daughter filaments. Thus, dissociation of Pi from the ADP-Pi transition state reduces the interactions of Arp2/3 complex with the actin filaments and may contribute to the lower mechanical stability of mature branch junctions with ADP bound to the Arps. Our structures also reveal that the mother filament in contact with Arp2/3 complex is slightly bent and twisted, consistent with the preference of Arp2/3 complex binding curved actin filaments. The small degree of twisting constrains models of actin filament mechanics.
Crustal permeability generated through microearthquakes is constrained by seismic moment
Authors: Yu Pengliang , Mali Ankur , Velaga Thejasvi , Bi Alex , Yu Jiayi , Marone Chris , Shokouhi Parisa , Elsworth Derek 
Published: March 2024

AbstractWe link changes in crustal permeability to informative features of microearthquakes (MEQs) using two field hydraulic stimulation experiments where both MEQs and permeability evolution are recorded simultaneously. The Bidirectional Long Short-Term Memory (Bi-LSTM) model effectively predicts permeability evolution and ultimate permeability increase. Our findings confirm the form of key features linking the MEQs to permeability, offering mechanistically consistent interpretations of this association. Transfer learning correctly predicts permeability evolution of one experiment from a model trained on an alternate dataset and locale, which further reinforces the innate interdependency of permeability-to-seismicity. Models representing permeability evolution on reactivated fractures in both shear and tension suggest scaling relationships in which changes in permeability ($$\Delta k$$
Δ
k
) are linearly related to the seismic moment ($$M$$
M
) of individual MEQs as $$\Delta k\propto M$$
Δ
k
∝
M
. This scaling relation rationalizes our observation of the permeability-to-seismicity linkage, contributes to its predictive robustness and accentuates its potential in characterizing crustal permeability evolution using MEQs.
Spectral-temporal-spatial customization via modulating multimodal nonlinear pulse propagation
Authors: Qiu Tong , Cao Honghao , Liu Kunzan , Yu Li-Yu , Levy Manuel , Lendaro Eva , Wang Fan , You Sixian 
Published: March 2024

AbstractMultimode fibers (MMFs) are gaining renewed interest for nonlinear effects due to their high-dimensional spatiotemporal nonlinear dynamics and scalability for high power. High-brightness MMF sources with effective control of the nonlinear processes would offer possibilities in many areas from high-power fiber lasers, to bioimaging and chemical sensing, and to intriguing physics phenomena. Here we present a simple yet effective way of controlling nonlinear effects at high peak power levels. This is achieved by leveraging not only the spatial but also the temporal degrees of freedom during multimodal nonlinear pulse propagation in step-index MMFs, using a programmable fiber shaper that introduces time-dependent disorders. We achieve high tunability in MMF output fields, resulting in a broadband high-peak-power source. Its potential as a nonlinear imaging source is further demonstrated through widely tunable two-photon and three-photon microscopy. These demonstrations provide possibilities for technology advances in nonlinear optics, bioimaging, spectroscopy, optical computing, and material processing.
Water-dispersible X-ray scintillators enabling coating and blending with polymer materials for multiple applications
Authors: Zhang Hailei , Zhang Bo , Cai Chongyang , Zhang Kaiming , Wang Yu , Wang Yuan , Yang Yanmin , Wu Yonggang , Ba Xinwu , Hoogenboom Richard 
Published: March 2024

AbstractDeveloping X-ray scintillators that are water-dispersible, compatible with polymeric matrices, and processable to flexible substrates is an important challenge. Herein, Tb3+-doped Na5Lu9F32 is introduced as an X-ray scintillating material with steady-state X-ray light yields of 15,800 photons MeV−1, which is generated as nanocrystals on halloysite nanotubes. The obtained product exhibits good water-dispersibility and highly sensitive luminescence to X-rays. It is deposited onto a polyurethane foam to afford a composite foam material with dose-dependent radioluminescence. Moreover, the product is dispersed into polymer matrixes in aqueous solution to prepare rigid or flexible scintillator screen for X-ray imaging. As a third example, it is incorporated multilayer hydrogels for information camouflage and multilevel encryption. Encrypted information can be recognized only by X-ray irradiation, while the false information is read out under UV light. Altogether, we demonstrate that the water-dispersible scintillators are highly promising for aqueous processing of radioluminescent, X-ray imaging, and information encrypting materials.
Rectifying artificial nanochannels with multiple interconvertible permeability states
Authors: Qian Ruocan , Wu Mansha , Yang Zhenglin , Wu Yuting , Guo Weijie , Zhou Zerui , Wang Xiaoyuan , Li Dawei , Lu Yi 
Published: March 2024

AbstractTransmembrane channels play a vital role in regulating the permeation process, and have inspired recent development of biomimetic channels. Herein, we report a class of artificial biomimetic nanochannels based on DNAzyme-functionalized glass nanopipettes to realize delicate control of channel permeability, whereby the surface wettability and charge can be tuned by metal ions and DNAzyme-substrates, allowing reversible conversion between different permeability states. We demonstrate that the nanochannels can be reversibly switched between four different permeability states showing distinct permeability to various functional molecules. By embedding the artificial nanochannels into the plasma membrane of single living cells, we achieve selective transport of dye molecules across the cell membrane. Finally, we report on the advanced functions including gene silencing of miR-21 in single cancer cells and selective transport of Ca2+ into single PC-12 cells. In this work, we provide a versatile tool for the design of rectifying artificial nanochannels with on-demand functions.
BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer’s disease and other disorders of lipid-rich tissues
Authors: Podleśny-Drabiniok Anna , Novikova Gloriia , Liu Yiyuan , Dunst Josefine , Temizer Rose , Giannarelli Chiara , Marro Samuele , Kreslavsky Taras , Marcora Edoardo , Goate Alison Mary 
Published: March 2024

AbstractGenetic and experimental evidence suggests that Alzheimer’s disease (AD) risk alleles and genes may influence disease susceptibility by altering the transcriptional and cellular responses of macrophages, including microglia, to damage of lipid-rich tissues like the brain. Recently, sc/nRNA sequencing studies identified similar transcriptional activation states in subpopulations of macrophages in aging and degenerating brains and in other diseased lipid-rich tissues. We collectively refer to these subpopulations of microglia and peripheral macrophages as DLAMs. Using macrophage sc/nRNA-seq data from healthy and diseased human and mouse lipid-rich tissues, we reconstructed gene regulatory networks and identified 11 strong candidate transcriptional regulators of the DLAM response across species. Loss or reduction of two of these transcription factors, BHLHE40/41, in iPSC-derived microglia and human THP-1 macrophages as well as loss of Bhlhe40/41 in mouse microglia, resulted in increased expression of DLAM genes involved in cholesterol clearance and lysosomal processing, increased cholesterol efflux and storage, and increased lysosomal mass and degradative capacity. These findings provide targets for therapeutic modulation of macrophage/microglial function in AD and other disorders affecting lipid-rich tissues.
Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment
Authors: Yang Zhuo-Ran , Suo Huinan , Fan Jing-Wen , Lv Niannian , Du Kehan , Ma Teng , Qin Huimin , Li Yan , Yang Liu , Zhou Nuoya , Jiang Hao , Tao Juan , Zhu Jintao 
Published: March 2024

AbstractHypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.
Public perceptions and support of climate intervention technologies across the Global North and Global South
Authors: Baum Chad M. , Fritz Livia , Low Sean , Sovacool Benjamin K. 
Published: March 2024

AbstractNovel, potentially radical climate intervention technologies like carbon dioxide removal and solar geoengineering are attracting attention as the adverse impacts of climate change are increasingly felt. The ability of publics, particularly in the Global South, to participate in discussions about research, policy, and deployment is restricted amidst a lack of familiarity and engagement. Drawing on a large-scale, cross-country exercise of nationally representative surveys (N = 30,284) in 30 countries and 19 languages, this article establishes the first global baseline of public perceptions of climate-intervention technologies. Here, we show that Global South publics are significantly more favorable about potential benefits and express greater support for climate-intervention technologies. The younger age and level of climate urgency and vulnerability of these publics emerge as key explanatory variables, particularly for solar geoengineering. Conversely, Global South publics express greater concern that climate-intervention technologies could undermine climate-mitigation efforts, and that solar geoengineering could promote an unequal distribution of risks between poor and rich countries.
Supramolecular catalyst with [FeCl4] unit boosting photoelectrochemical seawater splitting via water nucleophilic attack pathway
Authors: Miao Jiaming , Lin Cheng , Yuan Xiaojia , An Yang , Yang Yan , Li Zhaosheng , Zhang Kan 
Published: March 2024

AbstractPropelled by the structure of water oxidation co-catalysts in natural photosynthesis, molecular co-catalysts have long been believed to possess the developable potential in artificial photosynthesis. However, the interfacial complexity between light absorber and molecular co-catalyst limits its structural stability and charge transfer efficiency. To overcome the challenge, a supramolecular scaffold with the [FeCl4] catalytic units is reported, which undergo a water-nucleophilic attack of the water oxidation reaction, while the supramolecular matrix can be in-situ grown on the surface of photoelectrode through a simple chemical polymerization to be a strongly coupled interface. A well-defined BiVO4 photoanode hybridized with [FeCl4] units in polythiophene reaches 4.72 mA cm−2 at 1.23 VRHE, which also exhibits great stability for photoelectrochemical seawater splitting due to the restraint on chlorine evolution reaction by [FeCl4] units and polythiophene. This work provides a novel solution to the challenge of the interface charge transfer of molecular co-catalyst hybridized photoelectrode.
Microtubule damage shapes the acetylation gradient
Authors: Andreu-Carbó Mireia , Egoldt Cornelia , Velluz Marie-Claire , Aumeier Charlotte 
Published: March 2024

AbstractThe properties of single microtubules within the microtubule network can be modulated through post-translational modifications (PTMs), including acetylation within the lumen of microtubules. To access the lumen, the enzymes could enter through the microtubule ends and at damage sites along the microtubule shaft. Here we show that the acetylation profile depends on damage sites, which can be caused by the motor protein kinesin-1. Indeed, the entry of the deacetylase HDAC6 into the microtubule lumen can be modulated by kinesin-1-induced damage sites. In contrast, activity of the microtubule acetylase αTAT1 is independent of kinesin-1-caused shaft damage. On a cellular level, our results show that microtubule acetylation distributes in an exponential gradient. This gradient results from tight regulation of microtubule (de)acetylation and scales with the size of the cells. The control of shaft damage represents a mechanism to regulate PTMs inside the microtubule by giving access to the lumen.
High-latitude platform carbonate deposition constitutes a climate conundrum at the terminal Mesoproterozoic
Authors: de Kock Michiel O. , Malatji Ingrit , Wabo Herve , Mukhopadhyay Joydip , Banerjee Amlan , Maré L. P. 
Published: March 2024

AbstractDuring the Mesoproterozoic Era, 1600 to 1000 million years ago, global climate was warm with very little evidence of glaciation. Substantial greenhouse warming would have been required to sustain this ice-free state given 5-18% lower solar luminosity. Paleomagnetic data reported here place voluminous ca. 1.2 Ga shallow marine carbonate deposits from India at an unexpectedly high latitude of around 70° from the equator. Previous studies noted high latitudes, but their implication was never considered. Here, we evaluate the temporal-latitudinal distribution of neritic carbonate deposits across the Proterozoic and identify similar deposits from North China that together with those from India are seemingly unique to the late Mesoproterozoic. A uniformitarian interpretation implies that this is cold-water carbonate deposition, but facies similarity with low-latitude neritic deposits rather suggests a hotter climate and elevated polar ocean temperatures of 15–20° or higher. This interpretation represents a climate conundrum that would require much greater greenhouse warming than documented for the Mesoproterozoic.
Dynamic enhancer landscapes in human craniofacial development
Authors: Rajderkar Sudha Sunil , Paraiso Kitt , Amaral Maria Luisa , Kosicki Michael , Cook Laura E. , Darbellay Fabrice , Spurrell Cailyn H. , Osterwalder Marco , Zhu Yiwen , Wu Han , Afzal Sarah Yasmeen , Blow Matthew J. , Kelman Guy , Barozzi Iros , Fukuda-Yuzawa Yoko , Akiyama Jennifer A. , Afzal Veena , Tran Stella , Plajzer-Frick Ingrid , Novak Catherine S. , Kato Momoe , Hunter Riana D. , von Maydell Kianna , Wang Allen , Lin Lin , Preissl Sebastian , Lisgo Steven , Ren Bing , Dickel Diane E. , Pennacchio Len A. , Visel Axel 
Published: March 2024

AbstractThe genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.
Orbitronics: light-induced orbital currents in Ni studied by terahertz emission experiments
Authors: Xu Yong , Zhang Fan , Fert Albert , Jaffres Henri-Yves , Liu Yongshan , Xu Renyou , Jiang Yuhao , Cheng Houyi , Zhao Weisheng 
Published: March 2024

AbstractOrbitronics is based on the use of orbital currents as information carriers. Orbital currents can be generated from the conversion of charge or spin currents, and inversely, they could be converted back to charge or spin currents. Here we demonstrate that orbital currents can also be generated by femtosecond light pulses on Ni. In multilayers associating Ni with oxides and nonmagnetic metals such as Cu, we detect the orbital currents by their conversion into charge currents and the resulting terahertz emission. We show that the orbital currents extraordinarily predominate the light-induced spin currents in Ni-based systems, whereas only spin currents can be detected with CoFeB-based systems. In addition, the analysis of the time delays of the terahertz pulses leads to relevant information on the velocity and propagation length of orbital carriers. Our finding of light-induced orbital currents and our observation of their conversion into charge currents opens new avenues in orbitronics, including the development of orbitronic terahertz devices.
Evolving copy number gains promote tumor expansion and bolster mutational diversification
Authors: Wang Zicheng , Xia Yunong , Mills Lauren , Nikolakopoulos Athanasios N. , Maeser Nicole , Dehm Scott M. , Sheltzer Jason M. , Sun Ruping 
Published: March 2024

AbstractThe timing and fitness effect of somatic copy number alterations (SCNA) in cancer evolution remains poorly understood. Here we present a framework to determine the timing of a clonal SCNA that encompasses multiple gains. This involves calculating the proportion of time from its last gain to the onset of population expansion (lead time) as well as the proportion of time prior to its first gain (initiation time). Our method capitalizes on the observation that a genomic segment, while in a specific copy number (CN) state, accumulates point mutations proportionally to its CN. Analyzing 184 whole genome sequenced samples from 75 patients across five tumor types, we commonly observe late gains following early initiating events, occurring just before the clonal expansion relevant to the sampling. These include gains acquired after genome doubling in more than 60% of cases. Notably, mathematical modeling suggests that late clonal gains may contain final-expansion drivers. Lastly, SCNAs bolster mutational diversification between subpopulations, exacerbating the circle of proliferation and increasing heterogeneity.
Gene expression analyses reveal differences in children’s response to malaria according to their age
Authors: Tebben Kieran , Yirampo Salif , Coulibaly Drissa , Koné Abdoulaye K. , Laurens Matthew B. , Stucke Emily M. , Dembélé Ahmadou , Tolo Youssouf , Traoré Karim , Niangaly Amadou , Berry Andrea A. , Kouriba Bourema , Plowe Christopher V. , Doumbo Ogobara K. , Lyke Kirsten E. , Takala-Harrison Shannon , Thera Mahamadou A. , Travassos Mark A. , Serre David 
Published: March 2024

AbstractIn Bandiagara, Mali, children experience on average two clinical malaria episodes per year. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, can vary dramatically among children. We simultaneously characterize host and parasite gene expression profiles from 136 Malian children with symptomatic falciparum malaria and examine differences in the relative proportion of immune cells and parasite stages, as well as in gene expression, associated with infection and or patient characteristics. Parasitemia explains much of the variation in host and parasite gene expression, and infections with higher parasitemia display proportionally more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child’s age also strongly correlates with variations in gene expression:Plasmodium falciparumgenes associated with age suggest that older children carry more male gametocytes, while variations in host gene expression indicate a stronger innate response in younger children and stronger adaptive response in older children. These analyses highlight the variability in host responses and parasite regulation duringP. falciparumsymptomatic infections and emphasize the importance of considering the children’s age when studying and treating malaria infections.