In-Cell Structural Biology by NMR: The Benefits of the Atomic Scale

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(10), P. 9497 - 9570

Published: March 31, 2022

In-cell structural biology aims at extracting information about proteins or nucleic acids in their native, cellular environment. This emerging field holds great promise and is already providing new facts outlooks of interest both fundamental applied levels. NMR spectroscopy has important contributions on this stage: It brings a broad variety nuclei the atomic scale, which ensures its versatility uniqueness. Here, we detail methods, knowledge, applications biomedical engineering related to in-cell by NMR. We finally propose brief overview main other techniques (EPR, smFRET, cryo-ET, etc.) draw some advisable developments for In era large-scale screenings deep learning, accurate qualitative experimental evidence are as essential ever understand interior life cells. can generate such it does so scale. review meant deliver comprehensive but accessible information, with advanced technical details reflections nature results, future field.

Language: Английский

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Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(1), P. 189 - 204

Published: Jan. 14, 2023

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology, as it represents a major obstacle to effective cancer treatment. Since cells are highly diverse at genetic, epigenetic, and phenotypic levels, intra-tumor can be assumed an important contributing factor nullification chemotherapeutic effects, recurrence tumor. Based on role heterogeneous subpopulations with varying cell-cycle dynamics behavior during progression treatment; herein, we aim establish comprehensive definition for adaptation neoplastic against therapy. We discuss two parallel yet distinct that play pivotal roles reducing effects chemotherapy: "resistant" "tolerant" populations. Furthermore, this review also highlights impact quiescent phase cell cycle survival mechanism cells. Beyond understanding mechanisms underlying quiescence, provides insightful perspective stem (CSCs) their dual intertwined functions based state response Moreover, CSCs, epithelial–mesenchymal transformed cells, circulating (CTCs), disseminated (DTCs), which mostly proved have multiple biological links implicated our viewpoint tumors. Overall, increasing knowledge key identifying new therapeutic solutions, emerging concept may provide us opportunities prevent dreadful recurrence.

Language: Английский

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Gene expression during the formation of resting spores induced by nitrogen starvation in the marine diatom Chaetoceros socialis

BMC Genomics, Journal Year: 2023, Volume and Issue: 24(1)

Published: March 10, 2023

Dormancy is widespread in both multicellular and unicellular organisms. Among diatoms, microalgae at the base of all aquatic food webs, several species produce dormant cells (spores or resting cells) that can withstand long periods adverse environmental conditions.We present first gene expression study during process spore formation induced by nitrogen depletion marine planktonic diatom Chaetoceros socialis. In this condition, genes related to photosynthesis nitrate assimilation, including high-affinity transporters (NTRs), were downregulated. While former result a common reaction among diatoms under stress, latter seems be exclusive spore-former C. The upregulation catabolic pathways, such as tricarboxylic acid cycle, glyoxylate cycle fatty beta-oxidation, suggests could use lipids source energy formation. Furthermore, lipoxygenase aldehyde dehydrogenases (ALDHs) advocates presence oxylipin-mediated signaling, while involved dormancy-related pathways conserved other organisms (e.g. serine/threonine-protein kinases TOR its inhibitor GATOR) provides interesting avenues for future explorations.Our results demonstrate transition from an active growth phase one characterized marked metabolic changes evidence signaling intercellular communication.

Language: Английский

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Nuclear Hsp104 safeguards the dormant translation machinery during quiescence

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 5, 2024

Abstract The resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic biosynthesis system. Here, we find age-associated metabolic cues target yeast disaggregase Hsp104 to maintain functional nuclear proteome during quiescence. switch respiratory metabolism accompanying decrease in translation rates direct interact latent initiation factor eIF2 suppress aggregation. Hindering from entering quiescent cells results delayed re-entry into cell cycle due compromised resumption synthesis. In sum, report cytosolic-nuclear partitioning is critical mechanism protect synthesis machinery quiescence yeast, ensuring rapid restart once nutrients are replenished.

Language: Английский

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Hypometabolism to survive the long polar night and subsequent successful return to light in the diatom Fragilariopsis cylindrus

New Phytologist, Journal Year: 2023, Volume and Issue: 241(5), P. 2193 - 2208

Published: Dec. 14, 2023

Diatoms, the main eukaryotic phytoplankton of polar marine regions, are essential for maintenance food chains specific to Arctic and Antarctic ecosystems, experiencing major disturbances under current climate change. As such, it is fundamental understand physiological mechanisms associated molecular basis their endurance during long night. Here, using diatom Fragilariopsis cylindrus, we report an integrative analysis combining transcriptomic, microscopic biochemical approaches shed light on strategies used survive We reveal that in prolonged darkness, cells enter a state quiescence with reduced metabolic transcriptional activity, which no cell division occurs. propose minimal energy provided by respiration degradation protein, carbohydrate lipid stores homeostasis maintained autophagy darkness. also internal structural changes manifest morphological acclimation including appearance large vacuole. Our results further show immediately following return light, able use photoprotective rapidly resume photosynthesis, demonstrating remarkable robustness diatoms darkness at low temperature.

Language: Английский

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Transcription factor networks in cellular quiescence

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

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Glucosinolates from Seed-Press Cake of Camelina sativa (L.) Crantz Extend Yeast Chronological Lifespan by Modulating Carbon Metabolism and Respiration

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 80 - 80

Published: Jan. 11, 2025

Glucosinolates (GSLs) are nitrogen/sulfur-containing glycosides widely present in the order of Brassicales, particularly Brassicaceae family. Camelina (Camelina sativa (L.) Crantz) is an oilseed plant belonging to this Its seeds, addition a distinctive fatty acid composition, contain three aliphatic GSLs: glucoarabin, glucocamelinin, and homoglucocamelinin. Our study explored impact these GSLs purified from press cake, by-product oil production, on yeast chronological aging, which established model for simulating aging post-mitotic quiescent mammalian cells. Supplementing cells with extends lifespan (CLS) dose-dependent manner. This enhancement relies improved mitochondrial respiration efficiency, resulting drastic decrease superoxide anion levels increase ATP production. Furthermore, GSL supplementation affects carbon metabolism. In particular, support pro-longevity preservation TCA cycle enzymatic activities enhanced glycerol catabolism. These changes contribute positively phosphorylating trehalose storage: both longevity-promoting prerequisites.

Language: Английский

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Unravelling the transcriptomic dynamics of Hyphopichia pseudoburtonii in co-culture with Botrytis cinerea

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316713 - e0316713

Published: Jan. 14, 2025

Hyphopichia pseudoburtonii , is emerging as a potential biocontrol agent against various phytopathogens. These traits have been attributed to the production of antifungal compounds in presence target pathogens. However, broad molecular mechanisms involved activity are not yet understood. This study employed RNA sequencing assess temporal changes H . Y963 gene expression patterns when co-cultivated with Botrytis cinerea Genes differentially expressed co-culture B compared monoculture were evaluated after 24, 48, and 120 h growth. Up-regulation genes encoding major core histones (H2A, H3, H4) ribosomes first 24 suggested an abundance cells S phase cell cycle. At 48 h, up-regulated highlight mitotic cycle induction filamentous growth, while later stages, up-regulation high affinity transporters sugars, copper iron, well those retention utilization siderophore-iron was evident. Altogether, data allude competition for space nutrients key activated research offers new insights into transcriptomic response illuminates adaptive strategies behind its activity.

Language: Английский

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The impact of phenotypic heterogeneity on fungal pathogenicity and drug resistance

FEMS Microbiology Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Phenotypic heterogeneity in genetically clonal populations facilitates cellular adaptation to adverse environmental conditions while enabling a return the basal physiological state. It also plays crucial role pathogenicity and acquisition of drug resistance unicellular organisms cancer cells, yet exact contributing factors remain elusive. In this review, we outline current state understanding concerning contribution phenotypic fungal pathogenesis antifungal resistance.

Language: Английский

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Multi-drug tolerance in Leishmania persister-like cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Leishmaniasis is caused by parasitic protozoa of the genus Leishmania and found widely across tropics sub-tropics, afflicting hundreds thousands people. The disease notoriously difficult to treat. Here, we present evidence existence persister-like cells in cultured populations, induced upon exposure normally lethal doses antimony, a used anti-leishmanial. Persisters are small fraction non-proliferative with reduced metabolism that adapted withstand variety environmental assaults, including antimicrobials. We show survive antimonials adopting quiescence phenotype characterised proliferation, constrained metabolism, diminished mitochondrial membrane potential. What more, these demonstrate cross-tolerance other anti-leishmanial drugs. Wild-type reverted similar levels drug susceptibility once antimony-induced pressure was removed. Surprisingly, which had previously been selected for genetic changes causing resistance antimony acquired level hyper-resistance after transient passage through quiescent state, without further change. Our results extreme versatility this eukaryotic pathogen adaptation highlight need development new anti-leishmanials targeting forms.

Language: Английский

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