bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Multiple Drivers of Environmental Change on Native and Invasive Macroalgae in Nearshore Groundwater Dependent Ecosystems
Authors: Okuhata B. K. , Delevaux J. M. S. , Richards Donà A. , Smith C. M. , Gibson V. L. , Dulai H. , El‐Kadi A. I. , Stamoulis K. , Burnett K. M. , Wada C. A. , Bremer L. L. 
Published: July 2023

AbstractGroundwater dependent ecosystems (GDE) are increasingly recognized as critical components of sustainable groundwater management, but are threatened by multiple drivers of environmental change. Despite this importance, data that link drivers of hydrologic change to GDEs are scarce. This study adapts a land‐sea modeling framework by calibrating marine models with macroalgal experiments to quantitatively assess impacts of climate and land use change on submarine groundwater discharge (SGD) and subsequent habitat suitability for a native (Ulva lactuca) and an invasive (Hypnea musciformis) macroalgae in nearshore GDEs in Kona, Hawai'i. Lab analyses demonstrate that while U. lactuca grows optimally in low‐salinity, high‐nutrient waters, H. musciformis appears constrained to a salinity threshold and exhibits low growth in low salinity despite high nutrient concentrations. Land‐sea model results predict that while a dry future climate (Representative Concentration Pathway 8.5 mid‐century) coupled with increased urban development will likely reduce SGD, protecting native forests may prevent further loss of SGD quantity. This prevention thus partially mitigates the decline in habitat suitability of U. lactuca due to the combined effects of climate and land use change. Findings also suggest that, in contrast to the native U. lactuca, reductions in SGD may favor H. musciformis growth if introduced to Kona. Collectively, this study demonstrates the importance of considering multiple drivers of environmental change on GDEs. This study bridges experiments with models to spatially map changes in species abundance beyond their current habitat conditions, and thus informs management actions that can explicitly incorporate future human and climate‐related impacts.
Single-cell transcriptomic profiles in the pathophysiology within the microenvironment of early diabetic kidney disease
Authors: Tsai Yi-Chun , Kuo Mei-Chuan , Huang Juan-Chi , Chang Wei-An , Wu Ling-Yu , Huang Yung-Chi , Chang Chao-Yuan , Lee Su-Chu , Hsu Ya-Ling 
Published: July 2023

AbstractDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, resulting in a huge socio-economic impact. Kidney is a highly complex organ and the pathogenesis underlying kidney organization involves complex cell-to-cell interaction within the heterogeneous kidney milieu. Advanced single-cell RNA sequencing (scRNA-seq) could reveal the complex architecture and interaction with the microenvironment in early DKD. We used scRNA-seq to investigate early changes in the kidney of db/m mice and db/db mice at the 14th week. Uniform Manifold Approximation and Projection were applied to classify cells into different clusters at a proper resolution. Weighted gene co-expression network analysis was used to identify the key molecules specifically expressed in kidney tubules. Information of cell–cell communication within the kidney was obtained using receptor-ligand pairing resources. In vitro model, human subjects, and co-detection by indexing staining were used to identify the pathophysiologic role of the hub genes in DKD. Among four distinct subsets of the proximal tubule (PT), lower percentages of proliferative PT and PT containing AQP4 expression (PTAQP4+) in db/db mice induced impaired cell repair activity and dysfunction of renin-angiotensin system modulation in early DKD. We found that ferroptosis was involved in DKD progression, and ceruloplasmin acted as a central regulator of the induction of ferroptosis in PTAQP4+. In addition, lower percentages of thick ascending limbs and collecting ducts with impaired metabolism function were also critical pathogenic features in the kidney of db/db mice. Secreted phosphoprotein 1 (SPP1) mediated pathogenic cross-talk in the tubular microenvironment, as validated by a correlation between urinary SPP1/Cr level and tubular injury. Finally, mesangial cell-derived semaphorin 3C (SEMA3C) further promoted endothelium-mesenchymal transition in glomerular endothelial cells through NRP1 and NRP2, and urinary SEMA3C/Cr level was positively correlated with glomerular injury. These data identified the hub genes involved in pathophysiologic changes within the microenvironment of early DKD.
Super-enhancer-driven MLX mediates redox balance maintenance via SLC7A11 in osteosarcoma
Authors: Guo Weitang , Wang Xin , Lu Bing , Yu Jiaming , Xu Mingxian , Huang Renxuan , Cheng Mingzhe , Yang Meiling , Zhao Wei , Zou Changye 
Published: July 2023

AbstractOsteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional addiction in cancer cells emphasizes the biological significance and clinical relevance of super-enhancers. In this study, we found that Max-like protein X (MLX), a member of the Myc-MLX network, is driven by super-enhancers. Upregulation of MLX predicts a poor prognosis in osteosarcoma. Knockdown of MLX impairs growth and metastasis of osteosarcoma in vivo and in vitro. Transcriptomic sequencing has revealed that MLX is involved in various metabolic pathways (e.g., lipid metabolism) and can induce metabolic reprogramming. Furthermore, knockdown of MLX results in disturbed transport and storage of ferrous iron, leading to an increase in the level of cellular ferrous iron and subsequent induction of ferroptosis. Mechanistically, MLX regulates the glutamate/cystine antiporter SLC7A11 to promote extracellular cysteine uptake required for the biosynthesis of the essential antioxidant GSH, thereby detoxifying reactive oxygen species (ROS) and maintaining the redox balance of osteosarcoma cells. Importantly, sulfasalazine, an FDA-approved anti-inflammatory drug, can inhibit SLC7A11, disrupt redox balance, and induce massive ferroptosis, leading to impaired tumor growth in vivo. Taken together, this study reveals a novel mechanism in which super-enhancer-driven MLX positively regulates SLC7A11 to meet the alleviated demand for cystine and maintain the redox balance, highlighting the feasibility and clinical promise of targeting SLC7A11 in osteosarcoma.
Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England
Authors: Perez-Guzman Pablo N. , Knock Edward , Imai Natsuko , Rawson Thomas , Santoni Cosmo Nazzareno , Alcada Joana , Whittles Lilith K. , Thekke Kanapram Divya , Sonabend Raphael , Gaythorpe Katy A. M. , Hinsley Wes , FitzJohn Richard G. , Volz Erik , Verity Robert , Ferguson Neil M. , Cori Anne , Baguelin Marc 
Published: July 2023

AbstractAs the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.4 (95% credible interval (CrI) 7.8-9.1). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (3.0%, 95% CrI 2.8-3.2), followed by Delta (2.1%, 95% CrI 1.9–2.4), Wildtype (1.2%, 95% CrI 1.1–1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.
Epigenetic mechanisms to propagate histone acetylation by p300/CBP
Authors: Kikuchi Masaki , Morita Satoshi , Wakamori Masatoshi , Sato Shin , Uchikubo-Kamo Tomomi , Suzuki Takehiro , Dohmae Naoshi , Shirouzu Mikako , Umehara Takashi 
Published: July 2023

AbstractHistone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which a p300/CREB-binding protein (CBP) multidomain monomer recognizes histone H4 N-terminal tail (NT) acetylation (ac) in a nucleosome and acetylates non-H4 histone NTs within the same nucleosome. p300/CBP not only recognized H4NTac via the bromodomain pocket responsible for reading, but also interacted with the DNA minor grooves via the outside of that pocket. This directed the catalytic center of p300/CBP to one of the non-H4 histone NTs. The primary target that p300 writes by reading H4NTac was H2BNT, and H2BNTac promoted H2A-H2B dissociation from the nucleosome. We propose a model in which p300/CBP replicates histone N-terminal tail acetylation within the H3-H4 tetramer to inherit epigenetic storage, and transcribes it from the H3-H4 tetramer to the H2B-H2A dimers to activate context-dependent gene transcription through local nucleosome destabilization.
Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella
Authors: Morreale Daniel P. , Porsch Eric A. , Kern Brad K. , St. Geme Joseph W. , Planet Paul J. 
Published: July 2023

AbstractThe bacterial genusKingellaincludes two pathogenic species, namelyKingella kingaeandKingella negevensis, as well as strictly commensal species. BothK. kingaeandK. negevensissecrete a toxin called RtxA that is absent in the commensal species. Here we present a phylogenomic study of the genusKingella, including new genomic sequences for 88 clinical isolates, genotyping of another 131 global isolates, and analysis of 52 available genomes. The phylogenetic evidence supports that the toxin-encoding operonrtxCAwas acquired by a common ancestor of the pathogenicKingellaspecies, and that a preexisting type-I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% ofK. kingaestrains containing two copies of thertxAtoxin gene. ThertxAduplication is largely clonal and is associated with invasive disease. Assays with isogenic strains show that a single copy ofrtxAis associated with reduced cytotoxicity in vitro. Thus, our study identifies key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer, co-option of an existing secretion system, and gene duplication.
Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma
Authors: Chen Xiao , Li Yinglu , Zhu Fang , Xu Xinjing , Estrella Brian , Pazos Manuel A. , McGuire John T. , Karagiannis Dimitris , Sahu Varun , Mustafokulov Mustafo , Scuoppo Claudio , Sánchez-Rivera Francisco J. , Soto-Feliciano Yadira M. , Pasqualucci Laura , Ciccia Alberto , Amengual Jennifer E. , Lu Chao 
Published: July 2023

AbstractInterplay between chromatin-associated complexes and modifications critically contribute to the partitioning of epigenome into stable and functionally distinct domains. Yet there is a lack of systematic identification of chromatin crosstalk mechanisms, limiting our understanding of the dynamic transition between chromatin states during development and disease. Here we perform co-dependency mapping of genes using CRISPR-Cas9-mediated fitness screens in pan-cancer cell lines to quantify gene-gene functional relationships. We identify 145 co-dependency modules and further define the molecular context underlying the essentiality of these modules by incorporating mutational, epigenome, gene expression and drug sensitivity profiles of cell lines. These analyses assign new protein complex composition and function, and predict new functional interactions, including an unexpected co-dependency between two transcriptionally counteracting chromatin complexes - polycomb repressive complex 2 (PRC2) and MLL-MEN1 complex. We show that PRC2-mediated H3K27 tri-methylation regulates the genome-wide distribution of MLL1 and MEN1. In lymphoma cells with EZH2 gain-of-function mutations, the re-localization of MLL-MEN1 complex drives oncogenic gene expression and results in a hypersensitivity to pharmacologic inhibition of MEN1. Together, our findings provide a resource for discovery of trans-regulatory interactions as mechanisms of chromatin regulation and potential targets of synthetic lethality.
Long-term durability of metastable β-Fe2O3 photoanodes in highly corrosive seawater
Authors: Liu Changhao , Zhang Ningsi , Li Yang , Fan Rongli , Wang Wenjing , Feng Jianyong , Liu Chen , Wang Jiaou , Hao Weichang , Li Zhaosheng , Zou Zhigang 
Published: July 2023

AbstractDurability is one prerequisite for material application. Photoelectrochemical decomposition of seawater is a promising approach to produce clean hydrogen by using solar energy, but it always faces the problem of serious Cl− corrosion. We find that the main deactivation mechanism of the photoanode is oxide surface reconstruction accompanied by the coordination of Cl− during seawater splitting, and the stability of the photoanode can be effectively improved by enhancing the metal-oxygen interaction. Taking the metastable β-Fe2O3 photoanode as an example, Sn added to the lattice can enhance the M–O bonding energy and hinder the transfer of protons to lattice oxygen, thereby inhibiting excessive surface hydration and Cl− coordination. Therefore, the bare Sn/β-Fe2O3 photoanode delivers a record durability for photoelectrochemical seawater splitting over 3000 h.
Enabling programmable dynamic DNA chemistry using small-molecule DNA binders
Authors: Xu Junpeng , Wang Guan Alex , Gao Lu , Wu Lang , Lei Qian , Deng Hui , Li Feng 
Published: July 2023

AbstractThe binding of small molecules to the double helical structure of DNA, through either intercalation or minor groove binding, may significantly alter the stability and functionality of DNA, which is a fundamental basis for many therapeutic and sensing applications. Here, we report that small-molecule DNA binders can also be used to program reaction pathways of a dynamic DNA reaction, where DNA strand displacement can be tuned quantitatively according to the affinity, charge, and concentrations of a given DNA binder. The binder-induced nucleic acid strand displacement (BIND) thus enables innovative technologies to accelerate the discovery and characterization of bioactive small molecules. Specifically, we demonstrate the comprehensive characterization of existing and newly discovered DNA binders, where critical parameters for binding affinity and sequence selectivity can be obtained in a single, unbiased molecular platform without the need for any specialized equipment. We also engineer a tandem BIND system as a high-throughput screening assay for discovering DNA binders, through which 8 DNA binders were successfully discovered from a library of 700 compounds.
In-sensor computing using a MoS2 photodetector with programmable spectral responsivity
Authors: Kwak Dohyun , Polyushkin Dmitry K. , Mueller Thomas 
Published: July 2023

AbstractOptical spectroscopy is an indispensable technique in almost all areas of scientific research and industrial applications. After its acquisition, an optical spectrum is usually further processed using a mathematical algorithm to classify or quantify the measurement results. Here we present the design and realization of a smart photodetector that provides such information directly without the need to explicitly record a spectrum. This is achieved by tailoring the spectral responsivity of the device to a specific purpose. In-sensor computation is performed at the lowest possible level of the sensor system hierarchy – the physical level of photon detection – and does not require any external processing of the measurement data. The device can be programmed to cover different types of spectral regression or classification tasks. We present the analysis of spectral mixtures as an example, but the scheme can also be applied to any other algorithm that can be represented by a linear operator. Our prototype physical implementation utilizes an ensemble of optical cavity-enhanced MoS2 photodetectors with different center wavelengths and individually adjustable peak responsivities. This spectroscopy method represents a significant advance in miniaturized and energy-efficient optical sensing.
Wearable bioelectronics fabricated in situ on skins
Authors: Ershad Faheem , Patel Shubham , Yu Cunjiang 
Published: July 2023

AbstractIn recent years, wearable bioelectronics has rapidly expanded for diagnosing, monitoring, and treating various pathological conditions from the skin surface. Although the devices are typically prefabricated as soft patches for general usage, there is a growing need for devices that are customized in situ to provide accurate data and precise treatment. In this perspective, the state-of-the-art in situ fabricated wearable bioelectronics are summarized, focusing primarily on Drawn-on-Skin (DoS) bioelectronics and other in situ fabrication methods. The advantages and limitations of these technologies are evaluated and potential future directions are suggested for the widespread adoption of these technologies in everyday life.
Life-long phishing attack detection using continual learning
Authors: Ejaz Asif , Mian Adnan Noor , Manzoor Sanaullah 
Published: July 2023

AbstractPhishing is an identity theft that employs social engineering methods to get confidential data from unwary users. A phisher frequently attempts to trick the victim into clicking a URL that leads to a malicious website. Many phishing attack victims lose their credentials and digital assets daily. This study demonstrates how the performance of traditional machine learning (ML)-based phishing detection models deteriorates over time. This failure is due to drastic changes in feature distributions caused by new phishing techniques and technological evolution over time. This paper explores continual learning (CL) techniques for sustained phishing detection performance over time. To demonstrate this behavior, we collect phishing and benign samples for three consecutive years from 2018 to 2020 and divide them into six datasets to evaluate traditional ML and proposed CL algorithms. We train a vanilla neural network (VNN) model in the CL fashion using deep feature embedding of HTML contents. We compare the proposed CL algorithms with the VNN model trained from scratch and with transfer learning (TL). We show that CL algorithms maintain accuracy over time with a tolerable deterioration of 2.45%. In contrast, VNN and TL-based models’ performance deteriorates by over 20.65% and 8%, respectively.
Estimating generation time of SARS-CoV-2 variants in Italy from the daily incidence rate
Authors: Lippiello Eugenio , Petrillo Giuseppe , Baccari Silvio , de Arcangelis Lucilla 
Published: July 2023

AbstractThe identification of the transmission parameters of a virus is fundamental to identify the optimal public health strategy. These parameters can present significant changes over time caused by genetic mutations or viral recombination, making their continuous monitoring fundamental. Here we present a method, suitable for this task, which uses as unique information the daily number of reported cases. The method is based on a time since infection model where transmission parameters are obtained by means of an efficient maximization procedure of the likelihood. Applying the method to SARS-CoV-2 data in Italy, we find an average generation time $${\overline{z}}=3.2 \pm 0.8$$

z
¯

=
3.2
±
0.8

days, during the temporal window when the majority of infections can be attributed to the Omicron variants. At the same time we find a significantly larger value $${\overline{z}}=6.2\pm 1.1$$

z
¯

=
6.2
±
1.1

days, in the temporal window when spreading was dominated by the Delta variant. We are also able to show that the presence of the Omicron variant, characterized by a shorter $${{\overline{z}}}$$

z
¯

, was already detectable in the first weeks of December 2021, in full agreement with results provided by sequences of SARS-CoV-2 genomes reported in national databases. Our results therefore show that the novel approach can indicate the existence of virus variants, resulting particularly useful in situations when information about genomic sequencing is not yet available. At the same time, we find that the standard deviation of the generation time does not significantly change among variants.
The animacy effect on free recall is equally large in mixed and pure word lists or pairs
Authors: Komar Gesa Fee , Mieth Laura , Buchner Axel , Bell Raoul 
Published: July 2023

AbstractThe cognitive mechanisms underlying the animacy effect on free recall have as yet to be identified. According to the attentional-prioritization account, animate words are better recalled because they recruit more attention at encoding than inanimate words. The account implies that the animacy effect should be larger when animate words are presented together with inanimate words in mixed lists or pairs than when animate and inanimate words are presented separately in pure lists or pairs. The present series of experiments served to systematically test whether list composition or pair composition modulate the animacy effect. In Experiment 1, the animacy effect was compared between mixed and pure lists. In Experiments 2 and 3, the words were presented in mixed or pure pairs to manipulate the direct competition for attention between animate and inanimate words at encoding. While encoding was intentional in Experiments 1 and 2, it was incidental in Experiment 3. In each experiment, a significant animacy effect was obtained, but the effect was equally large in mixed and pure lists or pairs of animate and inanimate words despite considerable sensitivity of the statistical test of the critical interaction. These findings provide evidence against the attentional-prioritization account of the animacy effect.