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1. Human adenovirus serotype 5 infection dysregulates cysteine, purine, and unsaturated fatty acid metabolism in fibroblasts

   https://doi.org/10.1096/fj.202402726R  

   Sanchez, Bailey‐J_C; Ortiz, Rudy_M; Grasis, Juris_A (March 2025, The FASEB Journal)

   Abstract Viral infections can cause cellular dysregulation of metabolic reactions. Viruses alter host metabolism to meet their replication needs. The impact of viruses on specific metabolic pathways is not well understood, even in well‐studied viruses, such as human adenovirus. Adenoviral infection is known to influence cellular glycolysis and respiration; however, global effects on overall cellular metabolism in response to infection are unclear. Furthermore, few studies have employed an untargeted approach, combining emphasis on viral dosage and infection. To address this, we employed untargeted metabolomics to quantify the dynamic metabolic shifts in fibroblasts infected with human adenovirus serotype 5 (HAdV‐5) at three dosages (0.5, 1.0, and 2.0 multiplicity of infection [MOI]) and across 4 time points (6‐, 12‐, 24‐, and 36‐h post‐infection [HPI]). The greatest differences in individual metabolites were observed at 6‐ and 12‐h post‐infection, correlating with the early phase of the HAdV‐5 infection cycle. In addition to its effects on glycolysis and respiration, adenoviral infection downregulates cysteine and unsaturated fatty acid metabolism while upregulating aspects of purine metabolism. These results reveal specific metabolic pathways dysregulated by adenoviral infection and the associated dynamic shifts in metabolism, suggesting that viral infections alter energetics via profound changes in lipid, nucleic acid, and protein metabolism. The results revealed previously unconsidered metabolic pathways disrupted by HAdV‐5 that can alter cellular metabolism, thereby prompting further investigation into HAdV mechanisms and antiviral targeting. 

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2. Green leaf volatiles co‐opt proteins involved in molecular pattern signalling in plant cells

   https://doi.org/10.1111/pce.14795  

   Tanarsuwongkul, Sasimonthakan; Fisher, Kirsten W.; Mullis, B. Todd; Negi, Harshita; Roberts, Jamie; Tomlin, Fallon; Wang, Qiang; Stratmann, Johannes W. (January 2024, Plant, Cell & Environment)

   Abstract The green leaf volatiles (GLVs)Z‐3‐hexen‐1‐ol (Z3‐HOL) andZ‐3‐hexenyl acetate (Z3‐HAC) are airborne infochemicals released from damaged plant tissues that induce defenses and developmental responses in receiver plants, but little is known about their mechanism of action. We found that Z3‐HOL and Z3‐HAC induce similar but distinctive physiological and signaling responses in tomato seedlings and cell cultures. In seedlings, Z3‐HAC showed a stronger root growth inhibition effect than Z3‐HOL. In cell cultures, the two GLVs induced distinct changes in MAP kinase (MAPK) activity and proton fluxes as well as rapid and massive changes in the phosphorylation status of proteins within 5 min. Many of these phosphoproteins are involved in reprogramming the proteome from cellular homoeostasis to stress and include pattern recognition receptors, a receptor‐like cytoplasmic kinase, MAPK cascade components, calcium signaling proteins and transcriptional regulators. These are well‐known components of damage‐associated molecular pattern (DAMP) signaling pathways. These rapid changes in the phosphoproteome may underly the activation of defense and developmental responses to GLVs. Our data provide further evidence that GLVs function like DAMPs and indicate that GLVs coopt DAMP signaling pathways. 

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3. Proteomic Profiling Reveals Roles of Stress Response, Ca ²⁺ Transient Dysregulation, and Novel Signaling Pathways in Alcohol‐Induced Cardiotoxicity

   https://doi.org/10.1111/acer.14471  

   Liu, Rui; Sun, Fangxu; Forghani, Parvin; Armand, Lawrence C.; Rampoldi, Antonio; Li, Dong; Wu, Ronghu; Xu, Chunhui (October 2020, Alcoholism: Clinical and Experimental Research)

   BackgroundAlcohol use in pregnancy increases the risk of abnormal cardiac development, and excessive alcohol consumption in adults can induce cardiomyopathy, contractile dysfunction, and arrhythmias. Understanding molecular mechanisms underlying alcohol‐induced cardiac toxicity could provide guidance in the development of therapeutic strategies. MethodsWe have performed proteomic and bioinformatic analysis to examine protein alterations globally and quantitatively in cardiomyocytes derived from human‐induced pluripotent stem cells (hiPSC‐CMs) treated with ethanol (EtOH). Proteins in both cell lysates and extracellular culture media were systematically quantitated. ResultsTreatment with EtOH caused severe detrimental effects on hiPSC‐CMs as indicated by significant cell death and deranged Ca²⁺handling. Treatment of hiPSC‐CMs with EtOH significantly affected proteins responsible for stress response (e.g., GPX1 and HSPs), ion channel‐related proteins (e.g. ATP1A2), myofibril structure proteins (e.g., MYL2/3), and those involved in focal adhesion and extracellular matrix (e.g., ILK and PXN). Proteins involved in the TNF receptor‐associated factor 2 signaling (e.g., CPNE1 and TNIK) were also affected by EtOH treatment. ConclusionsThe observed changes in protein expression highlight the involvement of oxidative stress and dysregulation of Ca²⁺handling and contraction while also implicating potential novel targets in alcohol‐induced cardiotoxicity. These findings facilitate further exploration of potential mechanisms, discovery of novel biomarkers, and development of targeted therapeutics against EtOH‐induced cardiotoxicity. 

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4. Feeding during hibernation shifts gene expression toward active season levels in brown bears (Ursus arctos)

   https://doi.org/10.1152/physiolgenomics.00030.2023  

   Perry, Blair W.; McDonald, Anna L.; Trojahn, Shawn; Saxton, Michael W.; Vincent, Ellery P.; Lowry, Courtney; Evans Hutzenbiler, Brandon D.; Cornejo, Omar E.; Robbins, Charles T.; Jansen, Heiko T.; et al (August 2023, Physiological genomics)

   Hibernation in bears involves a suite of metabolical and physiological changes, including the onset of insulin resistance, that are driven in part by sweeping changes in gene expression in multiple tissues. Feeding bears glucose during hibernation partially restores active season physiological phenotypes, including partial resensitization to insulin, but the molecular mechanisms underlying this transition remain poorly understood. Here, we analyze tissue-level gene expression in adipose, liver, and muscle to identify genes that respond to midhibernation glucose feeding and thus potentially drive postfeeding metabolical and physiological shifts. We show that midhibernation feeding stimulates differential expression in all analyzed tissues of hibernating bears and that a subset of these genes responds specifically by shifting expression toward levels typical of the active season. Inferences of upstream regulatory molecules potentially driving these postfeeding responses implicate peroxisome proliferator-activated receptor gamma (PPARG) and other known regulators of insulin sensitivity, providing new insight into high-level regulatory mechanisms involved in shifting metabolic phenotypes between hibernation and active states. 

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5. Subcellular proteomics for determining iron‐limited remodeling of plastids in the model diatom Thalassiosira pseudonana (Bacillariophyta)

   https://doi.org/10.1111/jpy.13379  

   Gomes, Kristofer_M; Nunn, Brook_L; Chappell, P_Dreux; Jenkins, Bethany_D (August 2023, Journal of Phycology)

   Abstract Diatoms are important primary producers in the world's oceans, yet their growth is constrained in large regions by low bioavailable iron (Fe). Low‐Fe stress‐induced limitation of primary production is due to requirements for Fe in components of essential metabolic pathways including photosynthesis and other chloroplast plastid functions. Studies have shown that under low‐Fe stress, diatoms alter plastid‐specific processes, including components of electron transport. These physiological changes suggest changes of protein content and in protein abundances within the diatom plastid. While in silico predictions provide putative information on plastid‐localized proteins, knowledge of diatom plastid proteins remains limited in comparison to well‐studied model photosynthetic organisms. To address this, we employed shotgun proteomics to investigate the proteome of subcellular plastid‐enriched fractions fromThalassiosira pseudonanato gain a better understanding of how the plastid proteome is remodeled in response to Fe limitation. Using mass spectrometry‐based peptide identification and quantification, we analyzedT. pseudonanagrown under Fe‐replete and ‐limiting conditions. Through these analyses, we inferred the relative quantities of each protein, revealing that Fe limitation regulates major metabolic pathways in the plastid, including the Calvin cycle. Additionally, we observed changes in the expression of light‐harvesting proteins. In silico localization predictions of proteins identified in this plastid‐enriched proteome allowed for an in‐depth comparison of theoretical versus observed plastid‐localization, providing evidence for the potential of additional protein import pathways into the diatom plastid. 

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