bluuebunny/crossref_metadata_2025_split huggingface dataset:
SLC13A2-transported citrate is a metabolic signal for PKM2 acetylation and degradation to suppress tumor growth
Authors: Qin Mengyao , Shi Li , Chen Hao , Liu Chan , Tang Zhiquan , An Donghao , Yu Wanting , He Dandan , Shao Chang , Yuan Shengtao , Yu Hong , Hao Haiping , Xiong Jing 
Published: May 2024

AbstractBackground and aimsMetabolic reprogramming represents as a pivotal hallmark for cancer, but TCA cycle in tumorigenesis and progression has long been neglected. Solute carrier (SLC) transporters mediate the transport of TCA cycle intermediates across membrane, but their functions in cancer pathogenesis remains unclear.Approaches & ResultsUsing integrated analysis of solute carrier (SLC) transporters for TCA cycle intermediates, we found that SLC13A2 was consistently downregulated in hepatocellular carcinoma (HCC) cells and liver tissues from human patients and heterogeneous mouse models. Adeno-associated virus (AAV)-transduced liver-specific knockout or overexpression of SLC13A2 promoted or ameliorated HCC progression in the primary mouse model, demonstrating that SLC13A2 served as a protective factor during HCC pathogenesis. SLC13A2 inhibited HCC cell proliferation by decreasing mitochondrial function via suppressed oxygen consumption and ATP production. Combined with metabolic flux analysis, we found that SLC13A2 imported citrate, which secreted acetyl-CoA as a precursor for the acetylation of pyruvate kinase muscle isozyme M2 (PKM2), which led to its protein degradation. Decreased activity of pyruvate kinase depleted pyruvate for the TCA cycle, thus inhibiting amino acid synthesis and nucleotide metabolism. Additionally, a decrease in nuclear PKM2 protein transduced to reprogrammed gene transcription for cell proliferation and metabolism which is required for tumor growth.ConclusionsThis study revealed that citrate transported by SLC13A2 acts as a signal to disrupt metabolic homeostasis for tumor growth and suggests potential drug targets for HCC therapy.graphic abstract
An Introductory Implementation of Breast Cancer Detection from Mammograms and Pixel Intensity with Efficient-Net Other Neural Nets
Authors: Banerjee Sheekar , Kabir Humayun 
Published: May 2024

AbstractIn the world of civilized medical scientific progression, cancer has become a very serious threat for the natural survival of human beings where breast cancer stays to be the second most dangerous type. Mostly women are embracing very pathetic death because of the delayed detection of the cancer cell in the certain period of their life. Machine Learning mechanism can definitely help at the stage of medical imaging which can escalate the diagnosis of the cancer cells at a very early age of its biological formation and development. We focused upon the deep learning approach to classify the normal and abnormal breast according to the medical imaging from the MIAS dataset of Mammograms and Pixel Intensity. The Convolution Neural Network (CNN) alongside ResNet, AmoebaNet and EfficientNet have been used for the detection with 330 mammograms in which 194 images are normal and 136 are having the identification of abnormal breasts. The accuracy of the entire experimental results was carrying the torch of potential legacy of deep learning in the medical imaging arena. The research is ongoing for the further development and optimization of CNN, AmoebaNet-C and EfficientNet architecture for the Pixel Intensity with higher accuracy, proper segmentation and masking. Source code of this research is available here:https://github.com/ac005sheekar/Breast-Cancer-Detection-with-Pixel-Intensity/
Evolutionary Systems Biology Identifies Genetic Trade-offs In Rice Defense Against Above- and Belowground Attackers
Authors: Dunivant Taryn S. , Godinez-Vidal Damaris , Perkins Craig , Lee Madelyn G. , Ta Matthew , Groen Simon C. 
Published: May 2024

AbstractLike other plants, wild and domesticated rice species (Oryza nivara, O. rufipogon, andO. sativa) evolve in environments with various biotic and abiotic stresses that fluctuate in intensity through space and time. Microbial pathogens and invertebrate herbivores such as plant-parasitic nematodes and caterpillars show geographical and temporal variation in activity patterns and may respond differently to certain plant defensive mechanisms. As such, plant interactions with multiple community members may result in conflicting selection pressures on genetic polymorphisms. Here, through assays with different above- and belowground herbivores, the fall armyworm (Spodoptera frugiperda) and the southern root-knot nematode (Meloidogyne incognita), respectively, and comparison with rice responses to microbial pathogens, we identify potential genetic trade-offs at theKSL8andMG1loci on chromosome 11.KSL8encodes the first committed step towards biosynthesis of either stemarane- or stemodane-type diterpenoids through the japonica (KSL8-jap) or indica (KSL8-ind) allele. Knocking outKSL8-japandCPS4, encoding an enzyme that acts upstream in diterpenoid synthesis, in japonica rice cultivars increased resistance toS. frugiperdaand decreased resistance toM. incognita. Furthermore,MG1resides in a haplotype that provided resistance toM. incognita, while alternative haplotypes are involved in mediating resistance to the rice blast fungusMagnaporthe oryzaeand other pests and pathogens. Finally,KSL8andMG1alleles are located within trans-species haplotypes and may be evolving under long-term balancing selection. Our data are consistent with a hypothesis that polymorphisms atKSL8andMG1may be maintained through complex and diffuse community interactions.
Homologous recombination promotes mitotic death to suppress the innate immune response
Authors: Szmyd Radoslaw , Casolin Sienna , French Lucy , Manjon Anna Gonzalez , Dhawan Andrew , Nelson Christopher B. , Cavalli Léa , Page Scott G. , Hau Eric , Pickett Hilda A. , Gee Harriet E. , Cesare Anthony J. 
Published: May 2024

ABSTRACTDouble strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Through single-cell analysis of extended live imaging, we unveiled how cell cycle-regulated DSB repair guides disparate mitotic catastrophe outcomes. Our data reveal that toxic double Holliday junctions (dHjs) generated during homologous recombination (HR) promote non-immunogenic intrinsic apoptosis in the immediate mitosis after S or G2-phase DSB induction. Conversely, the combined activity of non-homologous end joining (NHEJ), microhomology mediated end joining (MMEJ), and single strand annealing (SSA) enable G1 phase cells to tolerate high DSB loads at the cost of aberrant cell division, innate immune response activation and delayed extrinsic lethality. Targeting NHEJ, MMEJ, or SSA promotes HR-dependent mitotic death, while suppressing mitotic death fosters a robust immunogenic response. Together the data indicate that a temporal repair hierarchy, coupled with cumulative DSB load, serves as a reliable predictor of mitotic catastrophe outcomes. In this pathway, HR suppress the innate immune response by promoting mitotic lethality.
Efficiently determining membrane-bound conformations of peripheral membrane proteins using replica exchange with hybrid tempering
Authors: Natarajan Chandramouli , Srivastava Anand 
Published: May 2024

AbstractAccurately sampling the membrane-bound conformations of a peripheral membrane proteins (PMP) using classical all-atom molecular dynamics simulations (AAMD) is a formidable enterprise due to the rugged free energy landscape of the protein-membrane system. In general, AAMD-based extraction of binding geometry requires simulations of multiple systems with different initial user-defined binding poses that may not be exhaustive. As an alternative, advanced sampling methods are also applied to elucidate the membrane-binding mechanism of PMPs but these techniques are generally computationally expensive and often depend on choice of the collective variables (CV). In this work, we showcase the utility of CV-free replica exchange with hybrid tempering (REHT) method in capturing the membrane-bound conformations of PMPs by testing it on the Osh4 amphipathic lipid-packing sensor (ALPS) motif, a 27 amino-acid membrane binding peptide. We show that REHT samples all the membrane-bound conformations of the Osh4 ALPS peptide at their correct populations and does it in a highly efficient manner with minimum computational time. We clearly show that, out of the two significant conformations, the peptide prefers horizontal conformations over vertical ones. In both the conformations, REHT captures all the vital residue-wise membrane contacts. The transition between the two configuration is not uncommon as our calculations reveal a ∼ 2 kT free energy difference between the two conformations. Interestingly, from our simulations we also find that the transition from vertical to horizontal conformation involves limited unfolding the main helix’s last turn. From our findings, we conclude that REHT samples the membrane-bound conformations of Osh4 ALPS peptide very efficiently and also provides additional insights and information that are often not available with regular piece-wise AAMD simulations. The method can be used as an efficient tool to explore the membrane-binding mechanisms of PMPs.
Advancing microRNA Target Site Prediction with Transformer and Base-Pairing Patterns
Authors: Bi Yue , Li Fuyi , Wang Cong , Pan Tong , Davidovich Chen , Webb Geoffrey I. , Song Jiangning 
Published: May 2024

AbstractMicro RNAs (miRNAs) are short non-coding RNAs involved in various cellular processes, playing a crucial role in gene regulation. Identifying miRNA targets remains a central challenge and is pivotal for elucidating the complex gene regulatory networks. Traditional computational approaches have predominantly focused on identifying miRNA targets through perfect Watson-Crick base pairings within the seed region, referred to as canonical sites. However, emerging evidence suggests that perfect seed matches are not a prerequisite for miRNA-mediated regulation, underscoring the importance of also recognizing imperfect, or non-canonical, sites. To address this challenge, we propose Mimosa, a new computational approach that employs the Transformer framework to enhance the prediction of miRNA targets. Mimosa distinguishes itself by integrating contextual, positional, and base-pairing information to capture in-depth attributes, thereby improving its predictive capabilities. Its unique ability to identify non-canonical base-pairing patterns makes Mimosa a standout model, reducing the reliance on pre-selecting candidate targets. Mimosa achieves superior performance in gene-level predictions and also shows impressive performance in site-level predictions across various non-human species through extensive benchmarking tests. To facilitate research efforts in miRNA targeting, we have developed an easy-to-use web server for comprehensive end-to-end predictions, which is publicly available athttp://monash.bioweb.cloud.edu.au/Mimosa/.
Identifying weather patterns affecting household date palm sap consumption in Bangladesh, 2013-2016
Authors: Jackson Jules , Shanta Ireen Sultana , McKee Clifton , Luby Stephen P , Haider Najmul , Sharker Yushuf , Plowright Raina , Hudson Peter , Gurley Emily 
Published: May 2024

AbstractNipah virus spillovers via consumption of date palm sap in Bangladesh vary substantially between years and have been associated with lower winter temperatures and precipitation. However, the mechanisms driving the interannual variation and the influence of weather remain unexplained. Here we investigated the hypothesis that weather patterns change human sap consumption and explain interannual variation in observed spillovers. We analyzed responses from a nationally representative survey conducted among 10,000 households in Bangladesh in 2013-2016 on household date palm sap consumption and weather data for each division of Bangladesh, using logistic regression to examine whether sap consumption is associated with weather variability. We found significant associations of lower minimum temperatures and precipitation with increased household sap consumption during the sap harvesting season. This relationship was largely similar within all months and divisions, and strong associations of temperature (χ2(1, n =5,027) = 7.74,p< 0.01) and, independently, precipitation (χ2= 8.00,p< 0.01) remained strong after accounting for month, location, and annual sap season. Interannual variation in date palm sap consumption in Bangladesh is likely best explained by temperature and precipitation patterns, where colder, drier winter days pose a higher risk for Nipah virus spillover. The synthesis of approaches to determine the driving forces of seasonality in our study may be a valuable method for investigating seasonality in other zoonotic pathogens.
United States Life Expectancy Increased in 2023
Authors: Wetzler Harry 
Published: May 2024

AbstractFrom 2019 to 2021 life expectancy at birth in the United States (US) declined by approximately 2.45 years to values not seen since 1996. Although life expectancy increased in 2022, the 2019 levels were not regained. Abridged life tables for 2019 to 2023 were constructed for the total US population, females, and males using mortality data from the CDC WONDER Multiple Cause of Death database and Census Bureau Vintage population estimates. Life expectancy at birth in 2023 increased approximately 1 year compared to 2022. The increase at age 65 was about 0.6 years. The increases in 2022 and 2023 replaced approximately 76% of the pandemic-era declines.
Metabolic enzymes moonlight as selective autophagy receptors to protect plants against viral-induced cellular damage
Authors: Clavel Marion , Bianchi Anita , Kobylinska Roksolana , Groh Roan , Ma Juncai , Papareddy Ranjith K. , Grujic Nenad , Picchianti Lorenzo , Stewart Ethan , Schutzbier Michael , Stejskal Karel , de la Concepcion Juan Carlos , de Medina Hernandez Victor Sanchez , Voichek Yoav , Clauw Pieter , Gunis Joanna , Durnberger Gerhard , Muelders Jens Christian , Grimm Annett , Sedivy Arthur , Erhardt Mathieu , Vyboishchikov Victoria , Gao Peng , Lechner Esther , Vantard Emilie , Jez Jakub , Roitinger Elisabeth , Genschik Pascal , Kang Byung-Ho , Dagdas Yasin 
Published: May 2024

AbstractRNA viruses co-opt the host endomembrane system and organelles to build replication complexes for infection. How the host responds to these membrane perturbations is poorly understood. Here, we explore the autophagic response ofArabidopsis thalianato three viruses that hijack different cellular compartments. Autophagy is significantly induced within systemically infected tissues, its disruption rendering plants highly sensitive to infection. Contrary to being an antiviral defense mechanism as previously suggested, quantitative analyses of the viral loads established autophagy as a tolerance pathway. Further analysis of one of these viruses, the Turnip Crinkle Virus (TCV) that hijack mitochondria, showed that despite perturbing mitochondrial integrity, TCV does not trigger a typical mitophagy response. Instead, TCV and Turnip yellow mosaic virus (TYMV) infection activates a distinct selective autophagy mechanism, where oligomeric metabolic enzymes moonlight as selective autophagy receptors and degrade key executors of defense and cell death such as EDS1. Altogether, our study reveals an autophagy-regulated metabolic rheostat that gauges cellular integrity during viral infection and degrades cell death executors to avoid catastrophic amplification of immune signaling.
Evolutionary analysis of paired box gene family and biological function exploration ofLr.Pax7in lamprey(Lethenteron reissneri)
Authors: Nurmamat Ayqeqan , Yan Zihao , Jiang Yao , Guan Haoran , Zhuang Ruyu , Zhang Shuyuan , Zhou Yuesi , Xiu Min , Pang Ya , Li Ding , Zhao Liang , Liu Xin , Han Yinglun 
Published: May 2024

AbstractThePax(paired box)gene family comprises highly conserved transcription factors that play a crucial regulatory role in embryonic development, tissue morphogenesis, and cell differentiation. The gene family comprises of nine members, namelyPax1toPax9, each exhibiting distinct functionalities and expression patterns. Among the members of the Pax family,Pax7is particularly involved in key regulatory functions related to skeletal muscle development and satellite cell biology in vertebrates. However, the precise role ofPax7and its downstream targets in jawless vertebrates such as lamprey remains relatively understudied. Therefore, investigating the expression and function of lamprey’sPaxgenes holds significant value as a model organism for understanding developmental processes, evolution, and interactions with other vertebrates. In this study, we identifiedPax7inLethentero reissneriand multiple bioinformatics analyses suggested that it may represent the ancestral gene of thePax7shared among higher vertebrates. To further elucidate the function and regulatory mechanism ofPax7, we performed transcriptome sequencing analysis after silencingLr.Pax7expression which revealed alterations in metabolic processes along with associated genes(Plcy,Jagged2,Hes,Myod,Frizzled2,etc) involved in various immune pathways(Notch, Wnt, IL-17, TNF, etc), myogenesis process, adipocyte formation process consistent with those observed in higher vertebrates. Comparative studies between lamprey and high vertebrates could provide valuable insight into understanding the functional role ofPax7and its downstream targets across diverse biological process as well as disease states.
GenomicLinks: Deep learning predictions of 3D chromatin loops in the maize genome
Authors: Schlegel Luca , Bhardwaj Rohan , Shahryary Yadollah , Demirtürk Defne , Marand Alexandre P. , Schmitz Robert J. , Johannes Frank 
Published: May 2024

AbstractGene regulation in eukaryotes is partly shaped by the 3D organization of chro]matin within the cell nucleus. Distal interactions betweencis-regulatory elements and their target genes are widespread and many causal loci underlying heritable agricultural traits have been mapped to distal non-coding elements. The biology underlying chromatin loop formation in plants is poorly understood. Dissecting the sequence features that mediate distal interactions is an important step toward identifying putative molecular mechanisms. Here, we trained GenomicLinks, a deep learning model, to identify DNA sequence features predictive of 3D chromatin interactions in maize. We found that the presence of binding motifs of specific Transcription Factor classes, especially bHLH, are predictive of chromatin interaction specificities. Using anin silicomutagenesis approach we show the removal of these motifs from loop anchors leads to reduced interaction probabilities. We were able to validate these predictions with single-cell co-accessibility data from different maize genotypes that harbor natural substitutions in these TF binding motifs. GenomicLinks is currently implemented as an open-source web tool, which should facilitate its wider use in the plant research community.
TRPγ regulates lipid metabolism throughDh44neuroendocrine cells
Authors: Nath Dharmendra Kumar , Dhakal Subash , Lee Youngseok 
Published: May 2024

ABSTRACTUnderstanding how the brain controls nutrient storage is pivotal. Transient receptor potential (TRP) channels are conserved from insects to humans. They serve in detecting environmental shifts and in acting as internal sensors. Here, we found that a TRPγ mutant exhibited inDrosophila melanogasterare required for maintaining normal lipid and protein levels. In animals, lipogenesis and lipolysis control lipid levels in response to food availability. Lipids are mostly stored as triacylglycerol in the fat bodies (FBs) ofD. melanogaster. Interestingly,trpγdeficient mutants exhibited elevated TAG levels and our genetic data indicated thatDh44neurons are indispensable for normal lipid storage but not protein storage. Thetrpγmutants also exhibited reduced starvation resistance, which was attributed to insufficient lipolysis in the FBs. This could be mitigated by administering lipase or metformin orally, indicating a potential treatment pathway. Gene expression analysis indicated thattrpγknockout downregulatedbrummer, a key lipolytic gene, resulting in chronic lipolytic deficits in the gut and other fat tissues. The study also highlighted the role of specific proteins, including neuropeptide DH44 and its receptor DH44R2 in lipid regulation. Our findings provide insight into the broader question of how the brain and gut regulates nutrient storage.
Phenomics demonstrates cytokines additive induction of epithelial to mesenchymal transition
Authors: Boché Alphonse , Morel Mathieu , Kellouche Sabrina , Carreiras Franck , Lambert Ambroise 
Published: May 2024

AbstractEpithelial to Mesenchymal Transition (EMT) is highly plastic with a program where cells lose adhesion and become more motile. EMT heterogeneity is one of the factors for disease progression and chemoresistance in cancer. Omics characterizations are costly and challenging to use. We developed single cell phenomics with easy to use wide-field fluorescence microscopy. We analyse over 70000 cells and combined 51 features. Our simplistic pipeline allows efficient tracking of EMT plasticity, with a single statistical metric. We discriminate four high EMT plasticity cancer cell lines along the EMT spectrum. We test two cytokines, inducing EMT in all cell lines, alone or in combination. The single cell EMT metrics demonstrate the additive effect of cytokines combination on EMT independently of cell line EMT spectrum. Single cell phenomics is uniquely suited to characterize the cellular heterogeneity in response to complex microenvironment, and show potential for drug testing assays.
PS Poly: A chain tracing algorithm to determine persistence length and categorize complex polymers by shape
Authors: Conley Elizabeth A. , Schaefer Katherine G. , Davison Harrison C. , King Gavin M. 
Published: May 2024

AbstractThe fundamental molecules of life are polymers. Prominent examples include nucleic acids and proteins, both of which assume a vast array of mechanical properties and three-dimensional shapes. The persistence length represents a numerical value to classify the bending rigidity of individual polymers. The shape of a polymer, dictated by the topology of the polymer backbone - a line trace through the center of the polymer along the contour path – is also a critical metric. Common architectures include linear, ring-like or cyclic, and branched; combinations of these can also exist, as in complex polymer networks. Determination of persistence length and shape are largely informative to polymer function and stability in biological environments. Here we demonstrate PS Poly, a near-fully automated algorithm to obtain polymer persistence length and shape from single molecule images obtained in physiologically relevant fluid conditions via atomic force microscopy. The algorithm, which involves image reduction via skeletonization followed by end point and branch point detection via filtering, is capable of rapidly analyzing thousands of polymers with subpixel precision. Algorithm outputs were verified by analysis of deoxyribose nucleic acid, a very well characterized macromolecule. The utility of method was further demonstrated by application to a recently discovered polypeptide chain named candidalysin. This toxic protein segment polymerizes in solution and represents the first human fungal pathogen yet discovered. PS poly is a robust and general algorithm. It can be used to extract fundamental information about polymer backbone stiffness, shape, and more generally, polymerization mechanisms.