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Keeping Wavering Bonds: Deactivation-Induced Signaling by Reactive Electrophiles
Marcus. J. C. Long
,Yaren Karakoç
,Yimon Aye
Discovered ~60years ago, the lipid metabolite 4-hydroxynonenal (HNE) is linked to a plethora of macromolecular targets and biological functions. For a molecule that weighs 156Da and possesses a single H-bond donor, this is quite a feat. Despite its chemical simplicity, HNE contains an α,β-unsaturated aldehyde system, endowing it with the capability to react covalently with numerous biological functional groups and bestowing on it pleiotropic properties. Regardless of the specific entity engaging with HNE, it is covalent bond formation that has dominated thought on HNE behavior. Indeed, cells possess a flurry of detoxifying enzymes that convert HNE to less reactive chemicals lacking the α,β-unsaturated aldehyde. For instance, the cell can either reduce or oxidize the aldehyde within HNE, deactivating HNE’s chemical reactivity. Here, we discuss one of our recent papers that discovered that HNE can modify the detoxification enzyme, Cyp-33e1, in C. elegans, using a customized tissue-specific screen for HNE-sensor proteins. Consistent with concepts of active site partitioning, HNE also emerged as a substrate of Cyp-33e1. We next discovered that HNE changed lipid storage in worms in a Cyp-33e1-dependent manner. We proposed that the product of Cyp-33e1 detoxifying HNE was responsible for this change in lipid storage, and were able to show that 4-hydroxynonenoic acid (HNA), the product of Cyp-33e1 oxidation of HNE, causes this phenotype. We have dubbed this new signaling mode, “deactivation signaling”. It sets an important precedent for how the bioactivity of HNE is considered, and we discuss the ramifications of this result in the paper.
Discovered ~60years ago, the lipid metabolite 4-hydroxynonenal (HNE) is linked to a plethora of macromolecular targets and biological functions. For a molecule that weighs 156Da and possesses a single H-bond donor, this is quite a feat. Despite its chemical simplicity, HNE contains an α,β-unsaturated aldehyde system, endowing it with the capability to react covalently with numerous biological functional groups and bestowing on it pleiotropic properties. Regardless of the specific entity engaging with HNE, it is covalent bond formation that has dominated thought on HNE behavior. Indeed, cells possess a flurry of detoxifying enzymes that convert HNE to less reactive chemicals lacking the α,β-unsaturated aldehyde. For instance, the cell can either reduce or oxidize the aldehyde within HNE, deactivating HNE’s chemical reactivity. Here, we discuss one of our recent papers that discovered that HNE can modify the detoxification enzyme, Cyp-33e1, in C. elegans, using a customized tissue-specific screen for HNE-sensor proteins. Consistent with concepts of active site partitioning, HNE also emerged as a substrate of Cyp-33e1. We next discovered that HNE changed lipid storage in worms in a Cyp-33e1-dependent manner. We proposed that the product of Cyp-33e1 detoxifying HNE was responsible for this change in lipid storage, and were able to show that 4-hydroxynonenoic acid (HNA), the product of Cyp-33e1 oxidation of HNE, causes this phenotype. We have dubbed this new signaling mode, “deactivation signaling”. It sets an important precedent for how the bioactivity of HNE is considered, and we discuss the ramifications of this result in the paper.
Posted: 28 February 2026
Quality of Life of Family Caregivers in Home Care: Challenges and Perspectives During COVID-19
Kauane Vieira De Oliveira
,Luana Dos Santos Andrade
,Davi Vantini
,Laercio Da Silva Paiva
,Fernando Luiz Affonso Fonseca
,Rosangela Filipini
Posted: 28 February 2026
Severe Pneumococcal Pneumonia with Concurrent Rhinovirus/Enterovirus Infection Leading to Sepsis in an Occupationally Exposed Welder
Pavlina Peneva
,Greta Kossian
,Leon Nedelcev
,Richard Coveney
,Pavel Yordanov
,Valentina Dimitrova
,Petar Georgiev
,Nikoleta Mircheva
,Figen Mustafa
,Anton Antonov
+7 authors
Posted: 28 February 2026
Between Soviet Legacy and Bologna Ambitions: Barriers to Music Education Integration in Central Asia
Cheng Junru
,Kambarova Zhumagul Ularbaevna
,Toksobaev Bulat T.
Posted: 28 February 2026
Dual-Mode Adaptive AI Persona Recommendation for Blockchain Education: A Mixed-Methods Evaluation of the PITL System Based on Dreyfus Competency Levels
Buğra Ayan
,Mutlu Tahsin Üstündağ
Posted: 28 February 2026
Aerobic Treatment Units for Widespread On-Site Wastewater Treatment in Coastal Louisiana: Pollution, Policy, and Market-Based Solutions
Anmol Soni
,Banna Das
,Matthew Brand
,Aaron Bivins
Posted: 28 February 2026
Therapy-Induced Senescence Shapes Extracellular Matrix Niches and Fibroblast Function in Head and Neck Squamous Cell Carcinoma
Jetsy Montero-Vergara
,Piotr W Darski
,Amy L Harding
,Keith D Hunter
Posted: 28 February 2026
The Photoreceptors Phototropin 1 and Phytochrome B Mediate Moonlight Perception and Response in Arabidopsis thaliana
Sasank Sannidhi
,Jeevan R. Singiri
,Naveen Kumar Yarra
,Nurit Novoplansky
,Gideon Grafi
Posted: 28 February 2026
Safety Signals Detected for Multiple Vaccines for Infants
Darrell Ricke
Posted: 28 February 2026
The Relationship Between Career Plateau and Organizational Indifference in Iranian Sports Organizations. Case Study: Ilam Province Sports and Youth Departments
Mohammadhosein Shohani
,Navid Mahtab
Posted: 28 February 2026
The Scale Group: A Novel Abelian Group Structure on the Positive Reals With Connections to Zeta Functions and Prime Numbers
Raheb Ali Mohammed Saleh Aoudh
Posted: 28 February 2026
Symmetry and Symmetry Breaking in Pulsar Spin-Down Dynamics: Fractional Calculus, Non-Integer Braking Indices, and the Resolution of the Crab Pulsar Puzzle
Farrukh Ahmed Chishtie
,Sree Ram Valluri
Posted: 28 February 2026
Design and Cost Analysis of an Integrated Waste-to-Resource System for Textile SMEs
Talha Ibn Hafiz
Posted: 28 February 2026
Explainable Deep Learning Approaches for Dyslexia Detection in English and Arabic Handwriting Using Convolutional Neural Networks and Transfer Learning
Marwa Abu Najm
,Hamid Mukhtar
Posted: 28 February 2026
Wasserstein Generative Data Modeling for Robust Portfolio Optimization Under Distributional Uncertainty
Sumeng Huang
,Yingyi Shu
,Kan Zhou
,Shihao Sun
,Yingxin Ou
,Ruobing Yan
Posted: 28 February 2026
Mitochondrial Graph-Based Pan-Genome Analysis of Hypsizygus Marmoreus: Structural Variation, Adaptive Evolution and Its Implications for Germplasm Resource Improvement
Ruichen Ma
,Wenyun Li
,Yongmei Miao
,Ruiheng Yang
,Youran Shao
,Junjun Shang
,Yan Li
,Yuan Gao
,Dapeng Bao
,Yingying Wu
As semi-autonomous organelles, mitochondria function through the coordinated regulation of nuclear genomes and their own genetic material, primarily providing energy for eukaryotic organisms. Currently, high-throughput sequencing technologies have been used to resolve the mitochondrial genomes of various edible fungi. With advances in sequencing technology, species genome characterization has evolved from single genomes to pan-genomes. However, the application of pan-genomes for the analysis of edible mushroom mitochondrial genomes remains unexplored. In this study, we conducted a comparative mitochondrial genome analysis of 31 Hypsizygus marmoreus strains (4 newly sequenced monotypes and 27 public datasets). The results revealed that the mitochondrial genome sizes ranged from 98,284 to 111,087 bp, exhibiting significant structural diversity. This variation is primarily driven by dynamic changes in non-coding regions, particularly intronic polymorphisms in the cox1 gene. This study revealed that tRNA secondary structures exhibit atypical globular and elongated conformations alongside copy number variations. Additionally, codon usage showed a pronounced A/T bias, whereas core respiratory chain genes demonstrated an evolutionary pattern of strong purifying selection. Furthermore, the 31 mitochondrial genomes of H. marmoreus were identified 8 gene rearrangement patterns and 5 genetic clusters, and the pan-genome (220,364 bp, 217 nodes) captured abundant SNPs, InDels and structural variations. This study provides breeding-relevant genetic markers and a genomic framework for germplasm classification, genetic improvement and stress-resilient variety molecular breeding of Hypsizygus marmoreus.
As semi-autonomous organelles, mitochondria function through the coordinated regulation of nuclear genomes and their own genetic material, primarily providing energy for eukaryotic organisms. Currently, high-throughput sequencing technologies have been used to resolve the mitochondrial genomes of various edible fungi. With advances in sequencing technology, species genome characterization has evolved from single genomes to pan-genomes. However, the application of pan-genomes for the analysis of edible mushroom mitochondrial genomes remains unexplored. In this study, we conducted a comparative mitochondrial genome analysis of 31 Hypsizygus marmoreus strains (4 newly sequenced monotypes and 27 public datasets). The results revealed that the mitochondrial genome sizes ranged from 98,284 to 111,087 bp, exhibiting significant structural diversity. This variation is primarily driven by dynamic changes in non-coding regions, particularly intronic polymorphisms in the cox1 gene. This study revealed that tRNA secondary structures exhibit atypical globular and elongated conformations alongside copy number variations. Additionally, codon usage showed a pronounced A/T bias, whereas core respiratory chain genes demonstrated an evolutionary pattern of strong purifying selection. Furthermore, the 31 mitochondrial genomes of H. marmoreus were identified 8 gene rearrangement patterns and 5 genetic clusters, and the pan-genome (220,364 bp, 217 nodes) captured abundant SNPs, InDels and structural variations. This study provides breeding-relevant genetic markers and a genomic framework for germplasm classification, genetic improvement and stress-resilient variety molecular breeding of Hypsizygus marmoreus.
Posted: 28 February 2026
Comparative Study of the Effects of Carvacrol and P-Cymene on the Motor Activity of Rats and Movement of Caenorhabditis elegans
Oliver Stošić
,Dragana Medić
,Djordje S Marjanović
,Tihomir Marić
,Veljko Savić
,Jelena Nedeljković Trailović
,Nemanja Zdravković
,Saša M Trailović
Posted: 28 February 2026
Intelligent Analysis of Data Flows for Real-Time Classification of Traffic Incidents
Gary Reyes
,Roberto Tolozano-Benites
,Cristhina Ortega
,Christian Albia
,Laura Lanzarini
,Waldo Hasperué
,Dayron Rumbaut
,Julio Barzola-Monteses
Posted: 28 February 2026
Consideration of Correlations in Radiometric Measurements of the Environment
Steven W. Brown
,Maritoni A. Litorja
,Julia K. Marrs
,David W. Allen
Posted: 28 February 2026
A Holistic Approach to Physical Health: Integrating Exercise, Nutrition, Hydration, and Sleep for Optimal Well-Being
Adam J. Nelson
Posted: 28 February 2026
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