bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments
Authors: Ogawa Yuki , Lim Brian C. , George Shanu , Oses-Prieto Juan A. , Rasband Joshua M. , Eshed-Eisenbach Yael , Hamdan Hamdan , Nair Supna , Boato Francesco , Peles Elior , Burlingame Alma L. , Van Aelst Linda , Rasband Matthew N. 
Published: October 2023

AbstractAxon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we use antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin. To determine the distributions of the identified proteins, we use CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We identify Contactin-1 (Cntn1) as an AIS cell surface protein. Cntn1 is enriched at the AIS through interactions with Neurofascin and NrCAM. We further show that Cntn1 contributes to assembly of the AIS extracellular matrix, and regulates AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.
Microwave-induced conductance replicas in hybrid Josephson junctions without Floquet—Andreev states
Authors: Haxell Daniel Z. , Coraiola Marco , Sabonis Deividas , Hinderling Manuel , ten Kate Sofieke C. , Cheah Erik , Krizek Filip , Schott Rüdiger , Wegscheider Werner , Belzig Wolfgang , Cuevas Juan Carlos , Nichele Fabrizio 
Published: October 2023

AbstractLight–matter coupling allows control and engineering of complex quantum states. Here we investigate a hybrid superconducting–semiconducting Josephson junction subject to microwave irradiation by means of tunnelling spectroscopy of the Andreev bound state spectrum and measurements of the current–phase relation. For increasing microwave power, discrete levels in the tunnelling conductance develop into a series of equally spaced replicas, while the current–phase relation changes amplitude and skewness, and develops dips. Quantitative analysis of our results indicates that conductance replicas originate from photon assisted tunnelling of quasiparticles into Andreev bound states through the tunnelling barrier. Despite strong qualitative similarities with proposed signatures of Floquet–Andreev states, our study rules out this scenario. The distortion of the current–phase relation is explained by the interaction of Andreev bound states with microwave photons, including a non-equilibrium Andreev bound state occupation. The techniques outlined here establish a baseline to study light–matter coupling in hybrid nanostructures and distinguish photon assisted tunnelling from Floquet–Andreev states in mesoscopic devices.
Food amyloid fibrils are safe nutrition ingredients based on in-vitro and in-vivo assessment
Authors: Xu Dan , Zhou Jiangtao , Soon Wei Long , Kutzli Ines , Molière Adrian , Diedrich Sabine , Radiom Milad , Handschin Stephan , Li Bing , Li Lin , Sturla Shana J. , Ewald Collin Y. , Mezzenga Raffaele 
Published: October 2023

AbstractFood protein amyloid fibrils have superior technological, nutritional, sensorial, and physical properties compared to native monomers, but there is as yet insufficient understanding of their digestive fate and safety for wide consumption. By combining SDS-PAGE, ELISA, fluorescence, AFM, MALDI-MS, CD, microfluidics, and SAXS techniques for the characterization of β-lactoglobulin and lysozyme amyloid fibrils subjected to in-vitro gastrointestinal digestion, here we show that either no noticeable conformational differences exist between amyloid aggregates and their monomer counterparts after the gastrointestinal digestion process (as in β-lactoglobulin), or that amyloid fibrils are digested significantly better than monomers (as in lysozyme). Moreover, in-vitro exposure of human cell lines and in-vivo studies with C. elegans and mouse models, indicate that the digested fibrils present no observable cytotoxicity, physiological abnormalities in health-span, nor accumulation of fibril-induced plaques in brain nor other organs. These extensive in-vitro and in-vivo studies together suggest that the digested food amyloids are at least equally as safe as those obtained from the digestion of corresponding native monomers, pointing to food amyloid fibrils as potential ingredients for human nutrition.
Enabling giant thermopower by heterostructure engineering of hydrated vanadium pentoxide for zinc ion thermal charging cells
Authors: Li Zhiwei , Xu Yinghong , Wu Langyuan , Cui Jiaxin , Dou Hui , Zhang Xiaogang 
Published: October 2023

AbstractFlexible power supply devices provide possibilities for wearable electronics in the Internet of Things. However, unsatisfying capacity or lifetime of typical batteries or capacitors seriously limit their practical applications. Different from conventional heat-to-electricity generators, zinc ion thermal charging cells has been a competitive candidate for the self-power supply solution, but the lack of promising cathode materials has restricted the achievement of promising performances. Herein, we propose an attractive cathode material by rational heterostructure engineering of hydrated vanadium pentoxide. Owing to the integration of thermodiffusion and thermoextraction effects, the thermopower is significantly improved from 7.8 ± 2.6 mV K−1 to 23.4 ± 1.5 mV K−1. Moreover, an impressive normalized power density of 1.9 mW m−2 K−2 is achieved in the quasi-solid-state cells. In addition, a wearable power supply constructed by three units can drive the commercial health monitoring system by harvesting body heat. This work demonstrates the effectiveness of electrodes design for wearable thermoelectric applications.
Dynamic characterization and interpretation for protein-RNA interactions across diverse cellular conditions using HDRNet
Authors: Zhu Haoran , Yang Yuning , Wang Yunhe , Wang Fuzhou , Huang Yujian , Chang Yi , Wong Ka-chun , Li Xiangtao 
Published: October 2023

AbstractRNA-binding proteins play crucial roles in the regulation of gene expression, and understanding the interactions between RNAs and RBPs in distinct cellular conditions forms the basis for comprehending the underlying RNA function. However, current computational methods pose challenges to the cross-prediction of RNA-protein binding events across diverse cell lines and tissue contexts. Here, we develop HDRNet, an end-to-end deep learning-based framework to precisely predict dynamic RBP binding events under diverse cellular conditions. Our results demonstrate that HDRNet can accurately and efficiently identify binding sites, particularly for dynamic prediction, outperforming other state-of-the-art models on 261 linear RNA datasets from both eCLIP and CLIP-seq, supplemented with additional tissue data. Moreover, we conduct motif and interpretation analyses to provide fresh insights into the pathological mechanisms underlying RNA-RBP interactions from various perspectives. Our functional genomic analysis further explores the gene-human disease associations, uncovering previously uncharacterized observations for a broad range of genetic disorders.
Sensorimotor transformation underlying odor-modulated locomotion in walking Drosophila
Authors: Tao Liangyu , Wechsler Samuel P. , Bhandawat Vikas 
Published: October 2023

AbstractMost real-world behaviors – such as odor-guided locomotion - are performed with incomplete information. Activity in olfactory receptor neuron (ORN) classes provides information about odor identity but not the location of its source. In this study, we investigate the sensorimotor transformation that relates ORN activation to locomotion changes in Drosophila by optogenetically activating different combinations of ORN classes and measuring the resulting changes in locomotion. Three features describe this sensorimotor transformation: First, locomotion depends on both the instantaneous firing frequency (f) and its change (df); the two together serve as a short-term memory that allows the fly to adapt its motor program to sensory context automatically. Second, the mapping between (f, df) and locomotor parameters such as speed or curvature is distinct for each pattern of activated ORNs. Finally, the sensorimotor mapping changes with time after odor exposure, allowing information integration over a longer timescale.
ZFYVE28 mediates insulin resistance by promoting phosphorylated insulin receptor degradation via increasing late endosomes production
Authors: Yu Liang , Xu Mengchen , Yan Yupeng , Huang Shuchen , Yuan Mengmeng , Cui Bing , Lv Cheng , Zhang Yu , Wang Hongrui , Jin Xiaolei , Hui Rutai , Wang Yibo 
Published: October 2023

AbstractInsulin resistance is associated with many pathological conditions, and an in-depth understanding of the mechanisms involved is necessary to improve insulin sensitivity. Here, we show that ZFYVE28 expression is decreased in insulin-sensitive obese individuals but increased in insulin-resistant individuals. Insulin signaling inhibits ZFYVE28 expression by inhibiting NOTCH1 via the RAS/ERK pathway, whereas ZFYVE28 expression is elevated due to impaired insulin signaling in insulin resistance. While Zfyve28 overexpression impairs insulin sensitivity and causes lipid accumulation, Zfyve28 knockout in mice can significantly improve insulin sensitivity and other indicators associated with insulin resistance. Mechanistically, ZFYVE28 colocalizes with early endosomes via the FYVE domain, which inhibits the generation of recycling endosomes but promotes the conversion of early to late endosomes, ultimately promoting phosphorylated insulin receptor degradation. This effect disappears with deletion of the FYVE domain. Overall, in this study, we reveal that ZFYVE28 is involved in insulin resistance by promoting phosphorylated insulin receptor degradation, and ZFYVE28 may be a potential therapeutic target to improve insulin sensitivity.
CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients
Authors: Zarodniuk Maksym , Steele Alexander , Lu Xin , Li Jun , Datta Meenal 
Published: October 2023

AbstractExcessive deposition of extracellular matrix (ECM) is a hallmark of solid tumors; however, it remains poorly understood which cellular and molecular components contribute to the formation of ECM stroma in central nervous system (CNS) tumors. Here, we undertake a pan-CNS analysis of retrospective gene expression datasets to characterize inter- and intra-tumoral heterogeneity of ECM remodeling signatures in both adult and pediatric CNS disease. We find that CNS lesions – glioblastoma in particular – can be divided into two ECM-based subtypes (ECMhi and ECMlo) that are influenced by the presence of perivascular stromal cells resembling cancer-associated fibroblasts (CAFs). Ligand-receptor network analysis predicts that perivascular fibroblasts activate signaling pathways responsible for recruitment of tumor-associated macrophages and promotion of cancer stemness. Our analysis reveals that perivascular fibroblasts are correlated with unfavorable response to immune checkpoint blockade in glioblastoma and poor patient survival across a subset of CNS tumors. We provide insights into new stroma-driven mechanisms underlying immune evasion and immunotherapy resistance in CNS tumors like glioblastoma, and discuss how targeting these perivascular fibroblasts may prove an effective approach to improving treatment response and patient survival in a variety of CNS tumors.
Benchmarking quantum logic operations relative to thresholds for fault tolerance
Authors: Hashim Akel , Seritan Stefan , Proctor Timothy , Rudinger Kenneth , Goss Noah , Naik Ravi K. , Kreikebaum John Mark , Santiago David I. , Siddiqi Irfan 
Published: October 2023

AbstractContemporary methods for benchmarking noisy quantum processors typically measure average error rates or process infidelities. However, thresholds for fault-tolerant quantum error correction are given in terms of worst-case error rates—defined via the diamond norm—which can differ from average error rates by orders of magnitude. One method for resolving this discrepancy is to randomize the physical implementation of quantum gates, using techniques like randomized compiling (RC). In this work, we use gate set tomography to perform precision characterization of a set of two-qubit logic gates to study RC on a superconducting quantum processor. We find that, under RC, gate errors are accurately described by a stochastic Pauli noise model without coherent errors, and that spatially correlated coherent errors and non-Markovian errors are strongly suppressed. We further show that the average and worst-case error rates are equal for randomly compiled gates, and measure a maximum worst-case error of 0.0197(3) for our gate set. Our results show that randomized benchmarks are a viable route to both verifying that a quantum processor’s error rates are below a fault-tolerance threshold, and to bounding the failure rates of near-term algorithms, if—and only if—gates are implemented via randomization methods which tailor noise.
The modular biochemical reaction network structure of cellular translation
Authors: Cuevas-Zuviría Bruno , Fer Evrim , Adam Zachary R. , Kaçar Betül 
Published: October 2023

AbstractTranslation is an essential attribute of all living cells. At the heart of cellular operation, it is a chemical information decoding process that begins with an input string of nucleotides and ends with the synthesis of a specific output string of peptides. The translation process is interconnected with gene expression, physiological regulation, transcription, and responses to signaling molecules, among other cellular functions. Foundational efforts have uncovered a wealth of knowledge about the mechanistic functions of the components of translation and their many interactions between them, but the broader biochemical connections between translation, metabolism and polymer biosynthesis that enable translation to occur have not been comprehensively mapped. Here we present a multilayer graph of biochemical reactions describing the translation, polymer biosynthesis and metabolism networks of an Escherichia coli cell. Intriguingly, the compounds that compose these three layers are distinctly aggregated into three modes regardless of their layer categorization. Multimodal mass distributions are well-known in ecosystems, but this is the first such distribution reported at the biochemical level. The degree distributions of the translation and metabolic networks are each likely to be heavy-tailed, but the polymer biosynthesis network is not. A multimodal mass-degree distribution indicates that the translation and metabolism networks are each distinct, adaptive biochemical modules, and that the gaps between the modes reflect evolved responses to the functional use of metabolite, polypeptide and polynucleotide compounds. The chemical reaction network of cellular translation opens new avenues for exploring complex adaptive phenomena such as percolation and phase changes in biochemical contexts.
Genetics re-establish the utility of 2-methylhopanes as cyanobacterial biomarkers before 750 million years ago
Authors: Hoshino Yosuke , Nettersheim Benjamin J. , Gold David A. , Hallmann Christian , Vinnichenko Galina , van Maldegem Lennart M. , Bishop Caleb , Brocks Jochen J. , Gaucher Eric A. 
Published: October 2023

AbstractFossilized lipids offer a rare glimpse into ancient ecosystems. 2-Methylhopanes in sedimentary rocks were once used to infer the importance of cyanobacteria as primary producers throughout geological history. However, the discovery of hopanoid C-2 methyltransferase (HpnP) in Alphaproteobacteria led to the downfall of this molecular proxy. In the present study, we re-examined the distribution of HpnP in a new phylogenetic framework including recently proposed candidate phyla and re-interpreted a revised geological record of 2-methylhopanes based on contamination-free samples. We show that HpnP was probably present in the last common ancestor of cyanobacteria, while the gene appeared in Alphaproteobacteria only around 750 million years ago (Ma). A subsequent rise of sedimentary 2-methylhopanes around 600 Ma probably reflects the expansion of Alphaproteobacteria that coincided with the rise of eukaryotic algae—possibly connected by algal dependency on microbially produced vitamin B12. Our findings re-establish 2-methylhopanes as cyanobacterial biomarkers before 750 Ma and thus as a potential tool to measure the importance of oxygenic cyanobacteria as primary producers on early Earth. Our study illustrates how genetics can improve the diagnostic value of biomarkers and refine the reconstruction of early ecosystems.
Stunting in infancy is associated with atypical activation of working memory and attention networks
Authors: Wijeakumar Sobanawartiny , Forbes Samuel H. , Magnotta Vincent A. , Deoni Sean , Jackson Kiara , Singh Vinay P. , Tiwari Madhuri , Kumar Aarti , Spencer John P. 
Published: October 2023

AbstractStunting is associated with poor long-term cognitive, academic and economic outcomes, yet the mechanisms through which stunting impacts cognition in early development remain unknown. In a first-ever neuroimaging study conducted on infants from rural India, we demonstrate that stunting impacts a critical, early-developing cognitive system—visual working memory. Stunted infants showed poor visual working memory performance and were easily distractible. Poor performance was associated with reduced engagement of the left anterior intraparietal sulcus, a region involved in visual working memory maintenance and greater suppression in the right temporoparietal junction, a region involved in attentional shifting. When assessed one year later, stunted infants had lower problem-solving scores, while infants of normal height with greater left anterior intraparietal sulcus activation showed higher problem-solving scores. Finally, short-for-age infants with poor physical growth indices but good visual working memory performance showed more positive outcomes suggesting that intervention efforts should focus on improving working memory and reducing distractibility in infancy.
DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages
Authors: Subudhi Amit Kumar , Green Judith L. , Satyam Rohit , Salunke Rahul P. , Lenz Todd , Shuaib Muhammad , Isaioglou Ioannis , Abel Steven , Gupta Mohit , Esau Luke , Mourier Tobias , Nugmanova Raushan , Mfarrej Sara , Shivapurkar Rupali , Stead Zenaida , Rached Fathia Ben , Ostwal Yogesh , Sougrat Rachid , Dada Ashraf , Kadamany Abdullah Fuaad , Fischle Wolfgang , Merzaban Jasmeen , Knuepfer Ellen , Ferguson David J. P. , Gupta Ishaan , Le Roch Karine G. , Holder Anthony A. , Pain Arnab 
Published: October 2023

AbstractMalaria-associated pathogenesis such as parasite invasion, egress, host cell remodelling and antigenic variation requires concerted action by many proteins, but the molecular regulation is poorly understood. Here we have characterized an essential Plasmodium-specific Apicomplexan AP2 transcription factor in Plasmodium falciparum (PfAP2-P; pathogenesis) during the blood-stage development with two peaks of expression. An inducible knockout of gene function showed that PfAP2-P is essential for trophozoite development, and critical for var gene regulation, merozoite development and parasite egress. Chromatin immunoprecipitation sequencing data collected at timepoints matching the two peaks of pfap2-p expression demonstrate PfAP2-P binding to promoters of genes controlling trophozoite development, host cell remodelling, antigenic variation and pathogenicity. Single-cell RNA sequencing and fluorescence-activated cell sorting revealed de-repression of most var genes in Δpfap2-p parasites. Δpfap2-p parasites also overexpress early gametocyte marker genes, indicating a regulatory role in sexual stage conversion. We conclude that PfAP2-P is an essential upstream transcriptional regulator at two distinct stages of the intra-erythrocytic development cycle.
Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin
Authors: Olafsson Sigurgeir , Rodriguez Elke , Lawson Andrew R. J. , Abascal Federico , Huber Axel Rosendahl , Suembuel Melike , Jones Philip H. , Gerdes Sascha , Martincorena Iñigo , Weidinger Stephan , Campbell Peter J. , Anderson Carl A. 
Published: October 2023

AbstractSomatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and nonlesional epidermis from 111 patients with psoriasis to search for evidence that somatic mutations in keratinocytes may influence the disease process. Lesional skin remained highly polyclonal, showing no evidence of large-scale spread of clones carrying potentially pathogenic mutations. The mutation rate of keratinocytes was similarly only modestly affected by the disease. We found evidence of positive selection in previously reported driver genes NOTCH1, NOTCH2, TP53, FAT1 and PPM1D and also identified mutations in four genes (GXYLT1, CHEK2, ZFP36L2 and EEF1A1) that we hypothesize are selected for in squamous epithelium irrespective of disease status. Finally, we describe a mutational signature of psoralens—a class of chemicals previously found in some sunscreens and which are used as part of PUVA (psoralens and ultraviolet-A) photochemotherapy treatment for psoriasis.
Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer
Authors: Trinidad Camille V. , Pathak Harsh B. , Cheng Shibo , Tzeng Shin-Cheng , Madan Rashna , Sardiu Mihaela E. , Bantis Leonidas E. , Deighan Clayton , Jewell Andrea , Rayamajhi Sagar , Zeng Yong , Godwin Andrew K. 
Published: October 2023

AbstractHigh grade serous ovarian carcinoma (HGSOC) accounts for ~ 70% of ovarian cancer cases. Non-invasive, highly specific blood-based tests for pre-symptomatic screening in women are crucial to reducing the mortality associated with this disease. Since most HGSOCs typically arise from the fallopian tubes (FT), our biomarker search focused on proteins found on the surface of extracellular vesicles (EVs) released by both FT and HGSOC tissue explants and representative cell lines. Using mass spectrometry, 985 EV proteins (exo-proteins) were identified that comprised the FT/HGSOC EV core proteome. Transmembrane exo-proteins were prioritized because these could serve as antigens for capture and/or detection. With a nano-engineered microfluidic platform, six newly discovered exo-proteins (ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF) plus a known HGSOC associated protein, FOLR1 exhibited classification performance ranging from 85 to 98% in a case–control study using plasma samples representative of early (including stage IA/B) and late stage (stage III) HGSOCs. Furthermore, by a linear combination of IGSF8 and ITGA5 based on logistic regression analysis, we achieved a sensitivity of 80% with 99.8% specificity and a positive predictive value of 13.8%. Importantly, these exo-proteins also can accurately discriminate between ovarian and 12 types of cancers commonly diagnosed in women. Our studies demonstrate that these lineage-associated exo-biomarkers can detect ovarian cancer with high specificity and sensitivity early and potentially while localized to the FT when patient outcomes are more favorable.