Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Ignacio J. Melero‐Jiménez, Yael Sorokin, Ami Merlin et al. · 2025 · Nature Communications
Populations facing lethal environmental change can escape extinction through rapid genetic adaptation, a process known as evolutionary rescue. Despite extensive study, evolutionary rescue is largely unexplored in mutualistic communities, where it is likely constrained by the less adaptable partner. Here, we explored empirically the likelihood, population dynamics, and genetic mechanisms underpinning evolutionary rescue in an obligate mutualism involving cross-feeding of amino acids between auxotrophic Escherichia coli strains. We found that over 80% of populations overcame a severe decline whe
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Zahraa S. Al-tameemi, Alejandra Rodríguez‐Verdugo · 2024 · mSystems
ABSTRACT Microbial communities are incredibly diverse. Yet, the eco-evolutionary processes originating and maintaining this diversity remain understudied. Here, we investigate the patterns of diversification for Pseudomonas putida evolving in isolation and with Acinetobacter johnsonii leaking resources used by P. putida . We experimentally evolved four experimental replicates in monoculture and co-culture for 200 generations. We observed that P. putida diversified into two distinct morphotypes that differed from their ancestor by single-point mutations. One of the most prominent mutations hit
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Leah Zuroff, Vista Farkhondeh, Riley Bove et al. · 2025 · Drugs
Despite major advances in multiple sclerosis (MS) treatment, disability accumulation independent of relapse activity remains a significant challenge. Chronic demyelination is a key driver of neurodegeneration and disease progression,…
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Mathieu Quinodoz, Kim Rodenburg, Zuzana Cvačková et al. · 2026 · Nature Genetics
Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP…
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Alicja W. Wojciechowska, Jakub W. Wojciechowski, Gert Vriend et al. · 2026 · Scientific Reports
Abstract While three-dimensional structures of globular and transmembrane forms are available for many amyloid proteins, structures of their amyloid forms are scarce in the PDB. Amyloids pose major challenges for both experimental…
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Valeriy Timofeyev, C. A. Porter, Dipika Tuteja et al. · 2010 · American Journal of Physiology-Heart and Circulatory Physiology
Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC(V) and AC(VI) are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy…
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Karsten Suhre, Qingwen Chen, Anna Halama et al. · 2025 · Nature Genetics
Most studies to date of protein quantitative trait loci (pQTLs) have relied on affinity proteomics platforms, which provide only limited information about the targeted protein isoforms and may be affected by genetic variation in their epitope binding. Here we show that mass spectrometry (MS)-based proteomics can complement these studies and provide insights into the role of specific protein isoform and epitope-altering variants. Using the Seer Proteograph nanoparticle enrichment MS platform, we identified and replicated new pQTLs in a genome-wide association study of proteins in blood plasma s
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Daniel S. Borrus, Raghav Sehgal, Judith Armstrong et al. · 2026 · Aging Cell
ABSTRACT Epigenetic clocks have emerged as potential biomarkers of aging due to their association with morbidity and mortality. They have recently gained traction as outcome measurements for anti‐aging interventions. However, as the number of new epigenetic clocks continues to grow, different clocks may not agree on the effect of an intervention. This raises the question of when researchers can trust epigenetic clock results. In this study, we find that when extending previously published single‐clock intervention studies to include additional clock models, no additional clocks reach statistic
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Marlee R. Labroo, Jessica Rutkoski · 2022 · BMC Genomics
BACKGROUND: Recurrent selection is a foundational breeding method for quantitative trait improvement. It typically features rapid breeding cycles that can lead to high rates of genetic gain. Usually, generations are discrete in recurrent selection, which means that breeding candidates are evaluated and considered for selection for only one cycle. Alternately, generations can overlap, with breeding candidates considered for selection as parents for multiple cycles. With recurrent genomic selection but not phenotypic selection, candidates can be re-evaluated by using genomic estimated breeding v
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Alexander A. Rashin, Marcin J. Domagalski, Michael T. Zimmermann et al. · 2014 · Acta Crystallographica Section D Biological Crystallography
Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to…
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Nikola Pavlović, Petar Todorović, Mirko Maglica et al. · 2025 · Biomolecules
The heart’s relentless contractile activity depends critically on mitochondrial function to meet its extraordinary bioenergetic demands. Mitochondria, through oxidative phosphorylation, not only supply ATP but also regulate metabolism, calcium homeostasis, and apoptotic signaling, ensuring cardiomyocyte viability and cardiac function. Mitochondrial dysfunction is a hallmark of cardiomyopathies and heart failure, characterized by impaired oxidative phosphorylation, excessive production of reactive oxygen species (ROS), dysregulated calcium handling, and disturbances in mitochondrial dynamics an
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Miruna C. Barbu, Carmen Amador, Alex S. F. Kwong et al. · 2022 · EBioMedicine
BACKGROUND: DNA methylation (DNAm) is associated with time-varying environmental factors that contribute to major depressive disorder (MDD) risk. We sought to test whether DNAm signatures of lifestyle and biochemical factors were associated with MDD to reveal dynamic biomarkers of MDD risk that may be amenable to lifestyle interventions. METHODS: , N=565), using CpG sites reported in previous well-powered methylome-wide association studies. We also compared their predictive accuracy for MDD to a MDD MS in an independent GS sub-sample (N=4,432). FINDINGS: =-0.069-0.083) remained significantly a
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Luyuan Chang, Yang Liu, Haipeng Li et al. · 2025 · Frontiers in Cellular and Infection Microbiology
Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid
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Ornella Zollo, Neal Sondheimer · 2017 · Transcription
In vitro studies of mitochondrial transcription often use linear templates that fail to replicate key features of transcription on a circular genome. We developed a plasmid-based system for the analysis of heavy-strand promoters that…
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Robert Massey, Yu Chen, Marina Panova‐Noeva et al. · 2024 · Cardiovascular Diabetology
BACKGROUND: BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability. METHODS: We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioreso
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Fanzhuo Xu, Yu Xie, Weiwei Yu et al. · 2026 · Frontiers in Microbiology
Multidrug resistance in Gram-negative bacteria has become a significant global public health challenge, threatening human health and clinical treatment outcomes. The unique outer membrane structure of these pathogens greatly limits antibiotic penetration, serving as the core mechanism of resistance. This paper systematically analyses antimicrobial strategies targeting the outer membrane of Gram-negative bacteria, mainly including: (1) directly disrupting the outer membrane structure and enhancing drug permeability; (2) inhibiting the biosynthesis or transport pathways of key outer membrane com
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Kristin Köppen, Diana Fatykhova, Gudrun Holland et al. · 2023 · Frontiers in Cellular and Infection Microbiology
Introduction Tularemia is mainly caused by Francisella tularensis ( Ft ) subsp. tularensis ( Ftt ) and Ft subsp. holarctica ( Ftt ) in humans and in more than 200 animal species including rabbits and hares. Human clinical manifestations depend on the route of infection and range from flu-like symptoms to severe pneumonia with a mortality rate up to 60% without treatment. So far, only 2D cell culture and animal models are used to study Francisella virulence , but the gained results are transferable to human infections only to a certain extent. Method In this study, we firstly established an ex
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Dingya Sun, Jialu Wang, Xin Li et al. · 2026 · Antioxidants
Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks-including glucose metabolism, amino acid metab
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Zhuoxu Gu, Zhonghao Wang, Xianquan Zhang et al. · 2025 · Frontiers in Pharmacology
As a modern dosage form of traditional Chinese medicine, Traditional Chinese Medicine Formula Granules (TCMFG) maximally retains active metabolites through standardized production processes, including dynamic countercurrent extraction and low-temperature concentration. This serves as a critical material basis for elucidating its multi-target regulatory mechanisms. Recent studies have highlighted the significant potential of TCMFG in treating complex diseases, such as inflammation, tumors, metabolic disorders, fibrosis, and orthopedic conditions like osteoarthritis and osteoporosis, by modulati
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Vasilios Liapis, Aneta Zysk, Mark DeNichilo et al. · 2017 · Cancer Medicine
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in
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Lorenzo Fant, Iuri Macocco, Jacopo Grilli · 2026 · PLoS Computational Biology
Microbial communities are taxonomically diverse and variable: species presence and abundances widely fluctuate over time, space, and even across biological replicates under controlled experimental conditions. However, environmental conditions exert strong selection on the traits of community members and their functions. Similar environmental conditions are expected to produce functionally similar communities. This environmental selection, combined with taxonomic variability, leads to the influential concept of functional redundancy - the idea that many species can perform the same function, al
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Marco Raffaele Cosenza, Alice Gaiatto, Büşra Erarslan Uysal et al. · 2025 · Nature
, the underlying processes and rates of spontaneous CA formation in human cells are underexplored. Here we introduce machine-learning-assisted genomics and imaging convergence (MAGIC)-an autonomously operated platform that integrates live-cell imaging of micronucleated cells, machine learning on-the-fly and single-cell genomics to systematically investigate CA formation. Applying MAGIC to near-diploid, non-transformed cell lines, we track de novo CAs over successive cell cycles, highlighting the common role of dicentric chromosomes as initiating events. We determine the baseline CA mutation ra
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Hiroki Isono, Taiju Miyagami, Kohta Katayama et al. · 2016 · Internal Medicine
Tetanus is a potentially fatal infection. Approximately 100 cases are reported in Japan each year; however, little is known about its clinical course and outcomes in the current era of treatment. We herein report three cases of tetanus in…
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Karin Hrovatin, Amir Ali Moinfar, Luke Zappia et al. · 2025 · BMC Genomics
Integration of single-cell RNA-sequencing (scRNA-seq) datasets is standard in scRNA-seq analysis. Nevertheless, current computational methods struggle to harmonize datasets across systems such as species, organoids and primary tissue, or different scRNA-seq protocols, including single-cell and single-nuclei. Conditional variational autoencoders (cVAE) are a popular integration method, however, existing strategies for stronger batch correction have limitations. Increasing the Kullback-Leibler divergence regularization does not improve integration and adversarial learning removes biological sign
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Hubert Krukowski, Sophie Valkenburg, A. Vich Vila et al. · 2026 · Nature Microbiology
Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study…
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Ryan H. Boe, Catherine G. Triandafillou, Rossana Lazcano et al. · 2026 · Genome biology
Abstract Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. We use spatial transcriptomics and single-cell RNA sequencing to uncover distinct resistance programs in melanoma cells shaped by intrinsic cellular states and the tumor microenvironment. Consensus non-negative matrix factorization reveals shared intrinsic resistance programs across cell lines. In patient samples, these resistance programs coexist within individual tumors and associate with diverse immune signatures. Single-cell resolution spatial transcriptomics in xenograft models reveals b
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Theresa Abdo, Ahmad Alhalabi, Sacha Yaghi et al. · 2026 · Cancer
Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA)…
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He Chen, Shaochen Yu, Mengjie Zhang et al. · 2026 · Frontiers in Immunology
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder resulting from a combination of genetic susceptibility, environmental factors, and an abnormal immune response of the intestinal immune system to commensal microorganisms. The gut microbiota and its metabolites play a pivotal role in maintaining intestinal immune homeostasis. Recent advances indicate that dysbiosis of the microbiota is accompanied by alterations in its metabolic functions. Abnormal levels of key metabolites, particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids, are clo
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Jiahui Lin, Zhongping Mao, Fei Yan · 2026 · Biosensors
Developing an ultrasensitive electrochemiluminescence (ECL) detection platform remains challenging due to the limited enrichment efficiency of ECL emitters and co-reactants at the electrode interface, as well as the insufficient catalytic enhancement of co-reactant conversion. Moreover, simultaneous in situ analyte enrichment and efficient anti-interference capability are often difficult to achieve in a single sensing interface. Herein, a new ECL platform was developed based on nanocatalyst-supported nanochannel-confined surfactant micelle (SM) system, which integrates an enhanced luminol-diss
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Sevgi Kundu, Senem Akkoç, Yalçın Erzurumlu et al. · 2026 · Molecular and Cellular Biochemistry
Abstract Within the scope of this investigation, two novel compounds ( 3a and 3b ) were designed and synthesized in two steps. Compounds 3a and 3b were tested utilizing the MTT study to evaluate their in vitro cytotoxic activity against healthy human embryonic kidney, lung cancer, breast cancer, and human liver cancer cell lines. It was determined that compound 3b exhibited high levels of cytotoxic activity against both liver and breast cancer cell lines, with IC 50 values of 10.83 and 11.55 µM, respectively. Also, to elucidate the anticancer mechanism of compounds, pro-apoptotic BAX and BiD ,
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