Science Advances

Journal Information
EISSN: 23752548
Total articles ≅ 10,136

Latest articles in this journal

Christopher T. Johns, , Alexandra Matthews, , M. Debora Iglesias-Rodriguez, , ,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.adc8728

Abstract:
Marine coccolithophores are globally distributed, unicellular phytoplankton that produce nanopatterned, calcite biominerals (coccoliths). These biominerals are synthesized internally, deposited into an extracellular coccosphere, and routinely released into the external medium, where they profoundly affect the global carbon cycle. The cellular costs and benefits of calcification remain unresolved. Here, we show observational and experimental evidence, supported by biophysical modeling, that free coccoliths are highly adsorptive biominerals that readily interact with cells to form chimeric coccospheres and with viruses to form “viroliths,” which facilitate infection. Adsorption to cells is mediated by organic matter associated with the coccolith base plate and varies with biomineral morphology. Biomineral hitchhiking increases host-virus encounters by nearly an order of magnitude and can be the dominant mode of infection under stormy conditions, fundamentally altering how we view biomineral-cell-virus interactions in the environment.
Yin Dai,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.adf8706

Abstract:
In the Mooser-Pearson diagram, binary ionic compoundss form into nonpolar symmetrical structures with high coordination numbers, while wurtzite structures should appear in the covalent region. Their tetrahedral bonding configurations break the inversion symmetry, with polarizations almost unswitchable due to the high barriers of abrupt breaking and reformation of covalent bonds. Here, through first-principles calculations, we find some exceptional cases of highly ionic ferroelectric binary salts such as lithium halides, which may form into wurtzite structures with covalent-like sp 3 bondings, and the origin of these abnormal formations is clarified. Their high polarizations induced by symmetry breaking are switchable, with much smoother switching pathway refrained from abrupt bond breaking due to the long-range feature of Coulomb interactions. These covalent-like ionic bondings do reduce not only their ferroelectric switching barriers but also the phase transition barriers between polar and nonpolar phases, rendering high performance in applications such as nonvolatile memory and energy storage.
Sam Dunkley,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.adc9161

Abstract:
Aging-related centromeric cohesion loss underlies premature separation of sister chromatids and egg aneuploidy in reproductively older females. Here, we show that F-actin maintains chromatid association after cohesion deterioration in aged eggs. F-actin disruption in aged mouse eggs exacerbated untimely dissociation of sister chromatids, while its removal in young eggs induced extensive chromatid separation events generally only seen in advanced reproductive ages. In young eggs containing experimentally reduced cohesion, F-actin removal accelerated premature splitting and scattering of sister chromatids in a microtubule dynamics–dependent manner, suggesting that actin counteracts chromatid-pulling spindle forces. Consistently, F-actin stabilization restricted scattering of unpaired chromatids generated by complete degradation of centromeric cohesion proteins. We conclude that actin mitigates egg aneuploidies arising from age-related cohesion depletion by limiting microtubule-driven separation and dispersion of sister chromatids. This is supported by our finding that spindle-associated F-actin structures are disrupted in eggs of reproductively older females.
Patrick Partscht, Alexander Simon, , ,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.add6982

Abstract:
Mitotic perturbations activate the spindle assembly checkpoint (SAC) that keeps cells in prometaphase with high CDK1 activity. Prolonged mitotic arrest is eventually bypassed by gradual cyclin B decline followed by slippage of cells into G 1 without chromosome segregation, a process that promotes cell transformation and drug resistance. Hitherto, the cyclin B1 decay is exclusively defined by mechanisms that involve its proteasomal degradation. Here, we report that hyperphosphorylated HIPK2 kinase accumulates in mitotic cells and phosphorylates the Rett syndrome protein MeCP2 at Ser 92 , a regulation that is counteracted by CDC14B phosphatase. MeCP2 S92 phosphorylation leads to the enhanced translation of cyclin B1, which is important for cells with persistent SAC activation to counteract the proteolytic decline of cyclin B1 and therefore to suspend mitotic slippage. Hence, the HIPK2/CDC14B-MeCP2 axis functions as an enhancer of the SAC-induced mitotic block. Collectively, our study revises the prevailing view of how cells confer a sustainable SAC.
, Manjunath G. Javoor, Julia Datler, Hermann Döring, Florian W. Hofer, , Victor-Valentin Hodirnau, Jan Faix, ,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.add6495

Abstract:
Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform–specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.
Lisa Kirchberger, Sreedeep Mukherjee, ,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.add2498

Abstract:
Neurons in the primary visual cortex (V1) respond to stimuli in their receptive field (RF), which is defined by the feedforward input from the retina. However, V1 neurons are also sensitive to contextual information outside their RF, even if the RF itself is unstimulated. Here, we examined the cortical circuits for V1 contextual responses to gray disks superimposed on different backgrounds. Contextual responses began late and were strongest in the feedback-recipient layers of V1. They differed between the three main classes of inhibitory neurons, with particularly strong contextual drive of VIP neurons, indicating a contribution of disinhibitory circuits to contextual drive. Contextual drive was strongest when the gray disk was perceived as figure, occluding its background, rather than a hole. Our results link contextual drive in V1 to perceptual organization and provide previously unknown insight into how recurrent processing shapes the response of sensory neurons to facilitate figure perception.
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.add8915

Abstract:
Establishing that climate exerts an important general influence on topography in tectonically active settings has proven an elusive goal. Here, we show that climates ranging from arid to humid consistently influence fluvial erosional efficiency and thus topography, and this effect is captured by a simple metric that combines channel steepness and mean annual rainfall, k snQ . Accounting for spatial rainfall variability additionally increases the sensitivity of channel steepness to lithologic and tectonic controls on topography, enhancing predictions of erosion and rock uplift rates, and supports the common assumption of a reference concavity near 0.5. In contrast, the standard channel steepness metric, k sn , intrinsically assumes that climate is uniform. Consequently, its use where rainfall varies spatially undermines efforts to distinguish climate from tectonic and lithologic effects, can bias reference concavity estimates, and may ultimately lead to false impressions about rock uplift patterns and other environmental influences. Capturing climate is therefore a precondition to understanding mountain landscape evolution.
Si Chen, Fangyuan Shao, Jianming Zeng, Sen Guo, Lijian Wang, Heng Sun, Josh Haipeng Lei, Xueying Lyu, Shuai Gao, Qiang Chen, et al.
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.abq1395

Abstract:
Breast cancer–associated gene 1 ( Brca1 ) deficiency induces the onset of breast cancer formation, accompanied with extensive genetic alterations. Here, we used both the sleeping beauty transposon mutagenesis system and CRISPR-Cas9–mediated genome-wide screening in mice to identify potential genetic alterations that act synergistically with Brca1 deficiency to promote tumorignesis. Both approaches identified Cullin-5 as a tumor suppressor, whose mutation enabled Brca1 -deficient cell survival and accelerated tumorigenesis by orchestrating tumor microenvironment. Cullin-5 suppresses cell growth through ubiquitylating and degrading adenosine 3′,5′-monophosphate–responsive element binding protein 1 (CREB1), especially under protein damage condition. Meanwhile, Cullin-5 deficiency activated CREB1-CCL2 signaling and resulted in the accumulation of monocytes and polymorphonuclear myeloid–derived suppressor cells, reduction of T cells that benefit tumor progression in both Brca1 -deficient cells and wild-type cells. Blocking CREB1 activity either through gene knockout or specific inhibitor treatment suppressed changes in the tumor microenvironment caused by Cullin-5 deficiency and blocked tumor progression.
, Derek R. Holman, AnaV Sood, Utkarsh Tandon, Salil S. Bhate, Sunil Bodapati, Graham L. Barlow, , Sarah Black, Erica C. Crenshaw, et al.
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.add1166

Abstract:
Although literature suggests that resistance to TNF inhibitor (TNFi) therapy in patients with ulcerative colitis (UC) is partially linked to immune cell populations in the inflamed region, there is still substantial uncertainty underlying the relevant spatial context. Here, we used the highly multiplexed immunofluorescence imaging technology CODEX to create a publicly browsable tissue atlas of inflammation in 42 tissue regions from 29 patients with UC and 5 healthy individuals. We analyzed 52 biomarkers on 1,710,973 spatially resolved single cells to determine cell types, cell-cell contacts, and cellular neighborhoods. We observed that cellular functional states are associated with cellular neighborhoods. We further observed that a subset of inflammatory cell types and cellular neighborhoods are present in patients with UC with TNFi treatment, potentially indicating resistant niches. Last, we explored applying convolutional neural networks (CNNs) to our dataset with respect to patient clinical variables. We note concerns and offer guidelines for reporting CNN-based predictions in similar datasets.
Yuan Gao, Feng Wang, , Eric Kutschera, Yang Xu, Stephan Xie, Yuanyuan Wang, Kathryn E. Kadash-Edmondson, Lan Lin,
Science Advances, Volume 9; https://doi.org/10.1126/sciadv.abq5072

Abstract:
Long-read RNA sequencing (RNA-seq) holds great potential for characterizing transcriptome variation and full-length transcript isoforms, but the relatively high error rate of current long-read sequencing platforms poses a major challenge. We present ESPRESSO, a computational tool for robust discovery and quantification of transcript isoforms from error-prone long reads. ESPRESSO jointly considers alignments of all long reads aligned to a gene and uses error profiles of individual reads to improve the identification of splice junctions and the discovery of their corresponding transcript isoforms. On both a synthetic spike-in RNA sample and human RNA samples, ESPRESSO outperforms multiple contemporary tools in not only transcript isoform discovery but also transcript isoform quantification. In total, we generated and analyzed ~1.1 billion nanopore RNA-seq reads covering 30 human tissue samples and three human cell lines. ESPRESSO and its companion dataset provide a useful resource for studying the RNA repertoire of eukaryotic transcriptomes.
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