bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silicocharacterization of five novel disease-resistance proteins inOryza sativa sp. japonicaagainst bacterial leaf blight and rice blast diseases
Authors: Dhiman Vedikaa , Biswas Soham , Shekhawat Rajveer Singh , Sadhukhan Ayan , Yadav Pankaj 
Published: June 2023

AbstractOryza sativasp.japonicais the most widely cultivated variety of rice. It has evolved several defense mechanisms, including PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI), which provide resistance against different pathogens to overcome biotic stresses. Several disease-resistance genes and proteins, such as R genes and PRR proteins, have been reported in the scientific literature which shows resistance againstXanthomonas oryzaepv.oryzae(Xoo), a causative agent for bacterial leaf blight disease (BB), andMagnaporthe oryzae(M. oryzae), causing rice blast disease (RB). Although some of these resistance proteins have been studied, the functional characterization of resistance proteins in rice is not exhaustive. In the current study, we identified five novel resistance proteins against BB and RB diseases through gene network analysis. Structure and function prediction, disease-resistance domain identification, protein-protein interaction (PPI), and pathway analysis revealed that the five new proteins played a role in the disease resistance against BB and RB.In silicomodeling, refinement, and model quality assessment were performed to predict the best structures of these five proteins, and submitted to ModelArchive for future use. The functional annotation of the proteins revealed their involvement in the bacterial disease resistance of rice. We predicted that the new resistance proteins could be localized to the nucleus and plasma membrane. This study provides insight into developing disease-resistant rice varieties by predicting novel candidate resistance proteins, which will pave the way for their future characterization and assist rice breeders in improving crop yield and addressing future food security.
Molecular Pixelation: Single cell spatial proteomics by sequencing
Authors: Karlsson Filip , Kallas Tomasz , Thiagarajan Divya , Karlsson Max , Schweitzer Maud , Navarro Jose Fernandez , Leijonancker Louise , Geny Sylvain , Pettersson Erik , Rhomberg-Kauert Jan , Granillo Marcela Gonzalez , Bunz Jessica , Dahlberg Johan , Simonetti Michele , Sathe Prajakta , Brodin Petter , Barrio Alvaro Martinez , Fredriksson Simon 
Published: June 2023

AbstractThe spatial distribution of cell surface proteins govern vital processes of the immune system such as inter-cell communication and mobility. However, tools for studying these at high multiplexing scale, resolution, and throughput needed to drive novel discoveries are lacking. We present Molecular Pixelation, a DNA-sequencing based method for single cell analysis to quantify protein abundance, spatial distribution, and colocalization of targeted proteins using Antibody Oligonucleotide Conjugates (AOCs). Relative locations of AOCs are inferred by sequentially associating these into local neighborhoods using DNA-pixels containing unique pixel identifier (UPI) sequences, forming >1,000 connected spatial zones per single cell in three dimensions. DNA-sequencing reads are computationally arranged into spatial single cell maps for 76 proteins without cell compartmentalization. By studying immune cell dynamics and using spatial statistics on graph representations of the data, previously known and novel patterns of protein spatial polarization and co-localization were found in chemokine-stimulated T-cells.
Ancient DNA reveals the origins of the Albanians
Authors: Davranoglou Leonidas-Romanos , Aristodemou Aris , Wesolowski David , Heraclides Alexandros 
Published: June 2023

AbstractThe origins of the Albanian people have vexed linguists and historians for centuries, as Albanians first appear in the historical record in the 11thcentury CE, while their language is one of the most enigmatic branches of the Indo-European family. To identify the populations that contributed to the ancestry of Albanians, we undertake a genomic transect of the Balkans over the last 8000 years, where we analyse more than 6000 previously published ancient genomes using state-of-the-art bioinformatics tools and algorithms that quantify spatiotemporal human mobility. We find that modern Albanians descend from Roman era western Balkan populations, with additional admixture from Slavic-related groups. Remarkably, Albanian paternal ancestry shows continuity from Bronze Age Balkan populations, including those known as Illyrians. Our results provide an unprecedented understanding of the historical and demographic processes that led to the formation of modern Albanians and help locate the area where the Albanian language developed.
Engineering cell and nuclear morphology on nano topography by contact-free protein micropatterning
Authors: Sarikhani Einollah , Meganathan Dhivya Pushpa , Rahmani Keivan , Tsai Ching-Ting , Marquez-Serrano Abel , Li Xiao , Santoro Francesca , Cui Bianxiao , Klausen Lasse Hyldgaard , Jahed Zeinab 
Published: June 2023

ABSTRACTPlatforms with nanoscale topography have recently become powerful tools in cellular biophysics and bioengineering. Recent studies have shown that nanotopography affects various cellular processes like adhesion and endocytosis, as well as physical properties such as cell shape.To engineer nanopillars more effectively for biomedical applications, it is crucial to gain better control and understanding of how nanopillars affect cell and nuclear physical properties, such as shape and spreading area, and impact cellular processes like endocytosis and adhesion. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate precise engineering of cellular architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, we discovered that cell elongation on nanopillars enhances nanopillar-induced endocytosis. These results have significant implications for various biomedical applications of nanopillars, including drug delivery, drug screening, intracellular electrophysiology, and biosensing. We believe our platform serves as a versatile tool for further explorations, facilitating investigations into the interplay between cell physical properties and alterations in cellular processes.Graphical Abstract
Enhanced expression of Dystrophin, IGF-1, CD44 and MYH3 in plasma and skeletal muscles including Diaphragm ofmdxmice after oral administration of Neu REFIX Beta 1,3-1,6 glucan
Authors: Preethy Senthilkumar , Sakamoto Shuji , Higuchi Takuma , Ichiyama Koji , Yamamoto Naoki , Ikewaki Nobunao , Iwasaki Masaru , Dedeepiya Vidyasagar Devaprasad , Srinivasan Subramaniam , Raghavan Kadalraja , Rajmohan Mathaiyan , Senthilkumar Rajappa , Abraham Samuel JK 
Published: June 2023

AbstractIntroductionDuchenne muscular dystrophy (DMD) is a rare genetic disease, causing muscle degeneration due to lack of dystrophin with inadequate muscle regeneration culminating in muscle dysfunction. The N-163 strain ofAureobasidium Pullulansproduced Beta-1,3-1,6-glucan (Neu REFIX) reported to be safe with anti-inflammatory and anti-fibrotic efficacy earlier, herein we evaluated its effects on muscle regeneration inmdxmice.MethodsForty-five mice in three groups (n=15 each): Group 1 (normal), Group 2 (mdxcontrol), and Group 3 (mdxfed Neu REFIX) were evaluated for 45 days. IGF-1, Dystrophin, CD44 and MYH3 in diaphragm, plasma and skeletal muscle were evaluated by ELISA and immunohistochemistry.ResultsMean IGF-1 expression was 20.32% and 16.27% higher in plasma (p = 0.03) and diaphragm respectively in Neu-REFIX group. Mean dystrophin was higher in Neu-REFIX group by 70.3% and 4.7% in diaphragm and plasma respectively than control. H-score intensity of CD44+ was >2.0 with an MYH3-positivity 20% higher in Neu-REFIX than control.ConclusionOral administration of Neu REFIX was safe. Significantly enhanced plasma IGF-1 beside increased Dystrophin, MYH3 and CD44, proving a restoration of muscle regeneration and differentiation, especially in diaphragm, makes us recommend it as a disease modifying adjuvant in both early and advanced stages of DMD.
Nest traits for the world’s birds
Authors: Sheard Catherine , Street Sally E. , Healy Susan D. , Troisi Camille A. , Clark Andrew D. , Yovcheva Antonia , Trébaol Alexis , Vanadzina Karina , Lala Kevin N. 
Published: June 2023

AbstractMotivationA well-constructed nest is a key element of successful reproduction in most species of birds, and nest-building strategies vary widely across the class. Macroecological and macroevolutionary studies tend to group nest design into a small number of discrete categories, often based on taxonomic inference. In reality, however, many species display considerable intraspecific variation in their nest-building behaviour, and broad-level categories may include many functionally distinct nest types. To address this confusion in the literature and facilitate future studies of broad-scale variation in avian parental care, we here introduce a detailed, global comparative database of nest building in birds, together with preliminary correlations between these traits and species-level environmental variables.Main types of variable containedWe present species-level data for nest structure, location, height, material composition, sex of builder, building time, and nest dimensions.Spatial location and grainGlobal. Maps are presented at the 1°x1° level.Time period and grainIncluded species are generally extant, although we present some data for recently extinct taxa. The data was collected 2017-2021 and was drawn from secondary sources published 1992-2021.Major taxa and level of measurementPartial or complete trait data is presented for 8,601 species of birds, representing 36 of 36 orders and 239 of 243 families.Software formatData have been uploaded as Supplementary Material in .xlsx format and are separated by species and source for all traits (S1) as well as summarised at the species level for structure and location variables (S2).
A genome-wide CRISPR screen in human prostate cancer cells reveals drivers of macrophage-mediated cell killing and positions AR as a tumor-intrinsic immunomodulator
Authors: Zaalberg Anniek , Minnee Emma , Mayayo-Peralta Isabel , Schuurman Karianne , Gregoricchio Sebastian , Schaik Thijs A. van , Hoekman Liesbeth , Li Dapei , Corey Eva , Janssen Hans , Lieftink Cor , Prekovic Stefan , Altelaar Maarten , Nelson Peter S. , Beijersbergen Roderick L. , Zwart Wilbert , Bergman Andries 
Published: June 2023

AbstractThe crosstalk between prostate cancer (PCa) cells and the tumor microenvironment plays a pivotal role in disease progression and metastasis and could provide novel opportunities for patient treatment. Macrophages are the most abundant immune cells in the prostate tumor microenvironment (TME) and are capable of killing tumor cells. To identify genes in the tumor cells that are critical for macrophage-mediated killing, we performed a genome-wide co-culture CRISPR screen and identified AR, PRKCD, and multiple components of the NF-κB pathway as hits, whose expression in the tumor cell are essential for being targeted and killed by macrophages. These data position AR signaling as an immunomodulator, and confirmed by androgen-deprivation experiments, that rendered hormone-deprived tumor cells resistant to macrophage-mediated killing. Proteomic analyses showed a downregulation of oxidative phosphorylation in thePRKCD-andIKBKG-KOcells compared to the control, suggesting impaired mitochondrial function, which was confirmed by electron microscopy analyses. Furthermore, phosphoproteomic analyses revealed that all hits impaired ferroptosis signaling, which was validated transcriptionally using samples from a neoadjuvant clinical trial with the AR-inhibitor enzalutamide.Collectively, our data demonstrate that AR functions together with the PRKCD and the NF-κB pathway to evade macrophage-mediated killing. As hormonal intervention represents the mainstay therapy for treatment of prostate cancer patients, our findings may have direct implications and provide a plausible explanation for the clinically observed persistence of tumor cells despite androgen deprivation therapy.
Human sodium current voltage-dependence at physiological temperature measured by coupling patch-clamp experiment to a mathematical model
Authors: Abrasheva Veronika O. , Kovalenko Sandaara G. , Slotvitsky Mihail , Scherbina Serafima A. , Aitova Aleria A. , Frolova Sheida , Tsvelaya Valeria , Syunyaev Roman A. 
Published: June 2023

AbstractVoltage-gated sodium channels are crucial to action potential propagation in excitable tissues. Voltage-clamp measurements of sodium current are very challenging and are usually performed at room temperature due to the high amplitude and fast activation of the current. In this study, we measured sodium current’s voltage dependence in stem-cell-derived cardiomyocytes at physiological temperature. Although apparent activation and inactivation curves measured as the sodium current amplitude dependence on voltage step is within the range reported in previous studies, we demonstrate a systematic error in our measurements that is due to deviation of membrane potential from the command potential of the amplifier. We show how this artifact can be accounted for by the computer simulation of the patch-clamp experiment. This patch-clamp model optimization technique yields a surprising result: −11.5 mV half-activation and −87 mV half-inactivation of the sodium current. Although the half-activation is strikingly different from what was previously believed to be typical for the cardiac sodium current, we show that this estimate explains conduction velocity dependence on extracellular potassium in hyperkalemic conditions.Key pointsVoltage gated sodium currents play a crucial role in excitable tissues including neurons, cardiac and skeletal muscles.Measurement of sodium current is challenging because of its high amplitude and rapid kinetics, especially at physiological temperature.We have used the patch-clamp technique to measure human sodium current voltage-dependence in human induced pluripotent stem cell-derived cardiomyocytes.The patch-clamp data was processed by optimization of the model accounting for voltage-clamp experiment artifacts, revealing a large difference between apparent parameters of sodium current and the results of the optimization.We conclude that actual sodium current activation is extremely depolarized in comparison to previous studies.The new sodium current model provides a better understanding of action potential propagation, we demonstrate that it explains propagation in hyperkalemic conditions.
OmicVerse: A single pipeline for exploring the entire transcriptome universe
Authors: Zeng Zehua , Ma Yuqing , Hu Lei , Liu Peng , Tan Bowen , Wang Yixuan , Xing Cencan , Xiong Yuanyan , Du Hongwu 
Published: June 2023

AbstractSingle-cell sequencing is frequently marred by “interruptions” due to limitations in sequencing throughput, yet bulk RNA-seq may harbor these ostensibly “interrupted” cells. In response, we introduce the single cell trajectory blending from Bulk RNA-seq (BulkTrajBlend) algorithm, a component of the OmicVerse suite that leverages a Beta-Variational AutoEncoder for data deconvolution and graph neural networks for the discovery of overlapping community. This approach proficiently interpolates and restores the continuity of “interrupted” cells within single-cell RNA sequencing dataset. Furthermore, OmicVerse provides an extensive toolkit for bulk and single cell RNA-seq analysis, offering uniform access to diverse methodologies, streamlining computational processes, fostering exquisite data visualization, and facilitating the extraction of novel biological insights to advance scientific research.
EZH2 inhibition promotes tumor immunogenicity in lung squamous cell carcinomas
Authors: DuCote Tanner J. , Song Xiulong , Naughton Kassandra J. , Chen Fan , Plaugher Daniel R. , Childress Avery R. , Edgin Abigail R. , Qu Xufeng , Liu Jinze , Liu Jinpeng , Li Fei , Wong Kwok-Kin , Brainson Christine F. 
Published: June 2023

ABSTRACTTwo important factors that contribute to resistance to immune checkpoint inhibitors (ICIs) are an immune-suppressive microenvironment and limited antigen presentation by tumor cells. In this study, we examine if inhibition of the methyltransferase EZH2 can increase ICI response in lung squamous cell carcinomas (LSCCs). Ourin vitroexperiments using 2D human cancer cell lines as well as 3D murine and patient derived organoids treated with two inhibitors of the EZH2 plus interferon-γ (IFNγ) showed that EZH2 inhibition leads to expression of both major histocompatibility complex class I and II (MHCI/II) expression at both the mRNA and protein levels. ChIP-sequencing confirmed loss of EZH2-mediated histone marks and gain of activating histone marks at key loci. Further, we demonstrate strong tumor control in models of both autochthonous and syngeneic LSCC treated with anti-PD1 immunotherapy with EZH2 inhibition. Single-cell RNA sequencing and immune cell profiling demonstrated phenotypic changes towards more tumor suppressive phenotypes in EZH2 inhibitor treated tumors. These results indicate that this therapeutic modality could increase ICI responses in patients undergoing treatment for LSCC.
Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 hours
Authors: Grenko Caleb M. , Bonnycastle Lori L. , Taylor Henry J. , Yan Tingfen , Swift Amy J. , Robertson Catherine C. , Narisu Narisu , Erdos Michael R. , Collins Francis S. , Taylor D. Leland 
Published: June 2023

AbstractDisruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycemia, beta cell glucotoxicity, and ultimately type 2 diabetes (T2D). In this study, we sought to explore the effects of hyperglycemia on human pancreatic islet (HPI) gene expression by exposing HPIs from two donors to low (2.8mM) and high (15.0mM) glucose concentrations over 24 hours, assaying the transcriptome at seven time points using single-cell RNA sequencing (scRNA-seq). We modeled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Across all cell types, we identified 1,528 genes associated with time, 1,185 genes associated with glucose exposure, and 845 genes associated with interaction effects between time and glucose. We clustered differentially expressed genes across cell types and found 347 modules of genes with similar expression patterns across time and glucose conditions, including two beta cell modules enriched in genes associated with T2D. Finally, by integrating genomic features from this study and genetic summary statistics for T2D and related traits, we nominate 363 candidate effector genes that may underlie genetic associations for T2D and related traits.
Transcription factor FfmA interacts both physically and genetically with AtrR to properly regulate gene expression in the fungusAspergillus fumigatus
Authors: Paul Sanjoy , Stamnes Mark A. , Moye-Rowley W. Scott 
Published: June 2023

AbstractTranscriptional regulation of azole resistance in the filamentous fungusAspergillus fumigatusis a key step in development of this problematic clinical phenotype. We and others have previously described a C2H2-containing transcription factor called FfmA that is required for normal levels of voriconazole susceptibility and expression of an ATP-binding cassette transporter gene calledabcG1. Null alleles offfmAexhibit a strongly compromised growth rate even in the absence of any external stress. Here we employ an acutely repressible doxycycline-off form offfmAto rapidly deplete FfmA protein from the cell. Using this approach, we carried out RNA-seq analyses to probe the transcriptome ofA. fumigatuscells that have been deprived of normal FfmA levels. We found that 2000 genes were differentially expressed upon depletion of FfmA, consistent with the wide-ranging effect of this factor on gene regulation. Chromatin immunoprecipitation coupled with high throughput DNA sequencing analysis (ChIP-seq) identified 530 genes that were bound by FfmA using two different antibodies for immunoprecipitation. More than 300 of these genes were also bound by AtrR demonstrating the striking regulatory overlap with FfmA. However, while AtrR is clearly an upstream activation protein with clear sequence specificity, our data suggest that FfmA is a chromatin-associated factor that may bind to DNA in a manner dependent on other factors. We provide evidence that AtrR and FfmA interact in the cell and can influence one another’s expression. This interaction of AtrR and FfmA is required for normal azole resistance inA. fumigatus.
Evaluating the capabilities of the Astral mass analyzer for single-cell proteomics
Authors: Petrosius Valdemaras , Aragon-Fernandez Pedro , Arrey Tabiwang N. , Üresin Nil , Furtwängler Benjamin , Stewart Hamish , Denisov Eduard , Petzoldt Johannes , Peterson Amelia C. , Hock Christian , Damoc Eugen , Makarov Alexander , Zabrouskov Vlad , Porse Bo T. , Schoof Erwin M. 
Published: June 2023

AbstractThe complexity of human physiology arises from well-orchestrated interactions between trillions of single cells in the body. While single-cell RNA sequencing (scRNA-seq) has enhanced our understanding of cell diversity, gene expression alone does not fully characterize cell phenotypes. Additional molecular dimensions, such as proteins, are needed to define cellular states accurately. Mass spectrometry (MS)-based proteomics has emerged as a powerful tool for comprehensive protein analysis, including single-cell applications. However, challenges remain in terms of throughput and proteomic depth, in order to maximize the biological impact of single-cell proteomics by Mass Spectrometry (scp-MS) workflows. This study leverages a novel high-resolution, accurate mass (HRAM) instrument platform, consisting of both an Orbitrap and an innovative HRAM Asymmetric Track Lossless (Astral) analyzer. The Astral analyzer offers high sensitivity and resolution through lossless ion transfer and a unique flight track design. We evaluate the performance of the Thermo Scientific Orbitrap Astral MS using Data-Independent Acquisition (DIA) and assess proteome depth and quantitative precision for ultra-low input samples. Optimal DIA method parameters for single-cell proteomics are identified, and we demonstrate the ability of the instrument to study cell cycle dynamics in Human Embryonic Kidney (HEK293) cells, and cancer cell heterogeneity in a primary Acute Myeloid Leukemia (AML) culture model.