Plants, being sessile organisms, have to endure unfavourable environmental conditions, thus they have developed exceptionally refined molecular systems that can sense, react and even recall stress signals. Stress memory, the ability to store information about previous stress treatments for faster and stronger reactions in the case of new exposures, is an indispensable adaptive mechanism that not only increases plant survival but also their overall fitness. Over the past few years, a considerable amount of evidence has been indicating the significance of epigenetic control in both the formation and the sustainability of stress memory, especially in the case of abiotic stress. This article presents an overview of the latest development on the epigenetic origin of plant stress memory with a focus on the mechanisms that play key role in the acclimatization to abiotic stress. The various molecular layers that are involved in the formation of stress memory viz. DNA methylation, chromatin remodelling, modifications of histones at post-translational level and the regulatory activities of non-coding RNAs have been elaborated. The stress specific epigenetic reactions due to abiotic stresses have been discussed to uncover regulatory attributes. Moreover, the review discusses the merging of cutting-edge technologies such as multi-omics tactics, the CRISPR/dCas9-targeted epigenome editing and machine learning solutions, with the aim of developing stress tolerant and high yielding crops. Despite the substantial progress made in identifying key epigenetic components, the major hurdles exist such as causal relationships being unclear, transgenerational stress memory over multiple generations being stable over time and eventually converting lab results into practical use in agriculture.
Somatic mutation generation is fundamental to cancer initiation, progression, heterogeneity, and treatment resistance, yet mutagenic capacity is often interpreted primarily through constitutive defects in DNA replication and genome-maintenance pathways. Emerging evidence indicates that the probability, rate, and spectrum of newly acquired mutations can also vary with cellular physiology and environmental context. This Review examines metabolic and mitochondrial alterations, oncogenic replication stress, transcriptional and chromatin-associated processes, inflammatory and enzymatic mutagenesis, tumor-microenvironmental pressures, and therapy-associated adaptation as potential determinants of mutation generation. We distinguish mutation generation from DNA damage, genomic instability, accumulated mutation burden, mutational topography, and clonal selection, and evaluate these mechanisms according to the strength of evidence linking cellular or environmental perturbations to subsequent mutation acquisition. Building on classical mutator phenotypes and prior concepts of stress-induced, adaptive, and therapy-associated mutagenesis, we propose the framework of dynamic mutator states: coordinated cellular configurations in which mutagenic capacity differs from an appropriate reference state through mechanistically identifiable processes and is accompanied by altered acquisition, rate, or spectrum of new mutations. Such states may be transient, recurrent, persistent, or progressively stabilized during tumor initiation, spatial diversification, metastatic evolution, treatment adaptation, residual disease, and relapse. We further define experimental criteria for identifying dynamic mutator states, emphasizing prospective mutation measurement, temporal ordering, lineage resolution, perturbation, and reversal or rescue. Finally, we consider whether mutation-generating processes themselves could become therapeutic targets, thereby limiting the supply of new genetic variation available for subsequent selection. A state-based view of mutagenesis provides a framework for connecting cellular physiology to mutation acquisition and for determining when mutation supply becomes a dynamic and potentially actionable component of cancer evolution.
IntroductionPresently, domestic geese remain genetically less studied farm animals. Goose breeding is a traditional branch of animal husbandry in Russia. Currently, the Russian goose gene pool includes 21 breeds of domestic and foreign origin; however, many populations have experienced a substantial decline and some are approaching extinction. Therefore, studies of genetic diversity and population structure are essential for developing effective conservation and breeding strategies aimed at preserving biodiversity.MethodsUsing 17 microsatellite (STR) markers, we investigated the genetic diversity and population structure of six Russian goose populations maintained exclusively in a conservation flock: Tula Fighting (TULA), Kholmogory White (KHLM_W), Kholmogory Gray (KHLM_G), Large Gray (LRGR), Vladimir Clay (VLDM), and Chinese Gray (CHGR). Genetic relationships among populations were analyzed to reconstruct genetic differentiation patterns and provide insights into their evolutionary history and conservation management.ResultsGenetic diversity indices varied considerably among populations. KHLM_W and KHLM_G exhibited the highest allelic richness (AR≥3.534 ± 0.260), whereas lower values were observed in the remaining populations (1.970 ± 0.213 in VLDM to 3.170 ± 0.193 in TULA). Expected heterozygosity (uHE) ranged between 0.191 ± 0.050 in VLDM and 0.599 ± 0.036 in KHLM_G. Among all populations, KHLM_G showed the highest polymorphism levels across diversity indicators (AR = 4.118 ± 0.196, HO = 0.457 ± 0.054, uHE = 0.599 ± 0.036). The inbreeding coefficient (uFIS) indicated a generally low extinction risk across populations, although VLDM demonstrated a potentially vulnerable status (0.258). PCA, Neighbor-Joining, Neighbor-Net, and STRUCTURE analyses consistently identified two major genetic clusters, with TULA or LRGR occupying an intermediate position depending on the analytical approach.DiscussionGenetic relationships inferred from microsatellite data were consistent with previous phenetic analyses and historical evidence regarding breed origins. Evolutionarily, CHGR and KHLM populations were associated with the Chinese lineage derived from the swan goose (Anser cygnoides), whereas LRGR represented the European lineage originating from the graylag goose (A. anser). Composite TULA and VLDM formed a European subgroup, while TULA also exhibited features of an intermediate lineage. These initial findings demonstrate that Russian goose populations represent unique genetic reservoirs containing valuable adaptive diversity and emphasize their importance for conservation and future breeding programs.
BackgroundlncRNAs served as crucial regulators in the pathogenesis and advancement of periodontitis. This study aimed to investigate whether lncRNA-FGD5-AS1 affects the proliferation and inflammatory response of LPS-induced HPDLSCs in vitro by regulating the miR-383-5p/SOCS3 axis.MethodTo set up an in vitro model of inflammation, HPDLSCs were treated with LPS. Cell proliferation, viability, gene expression (FGD5-AS1, miR-383-5p, and SOCS3), SOCS3 protein expression, and inflammatory cytokine levels were assessed by EdU staining, CCK-8, RT-qPCR, Western blot, and ELISA, respectively. Bioinformatics analysis, dual-luciferase reporter assays, RIP-qPCR, and RNA pull-down assays were further combined to verify the targeting relationships between miR-383-5p and SOCS3, and between FGD5-AS1 and miR-383-5p. Finally, oe-FGD5-AS1 and miR-383-5p mimic cell models were constructed to confirm that FGD5-AS1 regulated LPS-induced inflammatory injury via the miR-383-5p/SOCS3 axis.ResultsLPS exhibited a dose-dependent inhibitory effect on both the mRNA and protein levels of SOCS3 in HPDLSCs, and also inhibited cell proliferation. SOCS3 overexpression, in functional rescue experiments, was shown to lower the production of TNF-α, IL-1β, and IL-6 and rescue cell proliferation. At the mechanistic level, miR-383-5p directly targeted and downregulated SOCS3. Conversely, FGD5-AS1 served as a ceRNA that upregulated SOCS3 by sponging miR-383-5p. Functional experiments verified that FGD5-AS1 adsorbed miR-383-5p to relieve its inhibitory effect on SOCS3, thereby alleviating the inflammatory response induced by LPS, and exogenous addition of miR-383-5p could reverse this protective effect.ConclusionBy acting as a molecular sponge for miR-383-5p, FGD5-AS1 upregulates SOCS3 expression, thereby suppressing inflammation and enhancing the proliferative capacity of HPDLSCs in an in vitro model of LPS-induced periodontitis. These findings provide a novel theoretical framework for the epigenetic regulation of periodontitis and suggest that this axis may serve as a potential therapeutic target, which warrants further validation in appropriate in vivo models and clinical studies.
Dihydropyrimidine dehydrogenase (DPD, gene: DPYD) catalyzes the first step of pyrimidine catabolism. DPD deficiency contributes to a rare inborn error of metabolism associated with pediatric neurological manifestations that show wide variability in clinical presentation with incomplete penetrance (OMIM #274270). Common symptoms include autism spectrum disorder-like behaviors, ataxia, and global developmental delay, with variable involvement of seizures. In this report, we present one case of pediatric DPD deficiency accompanied by epilepsy-like syndromes, and a second case presenting with ataxia and dystonia in carriers of the deleterious DPYD c.1905+1G>A variant (rs3918290, DPYD*2A, ClinVar #432). One subject also carried a variant in the KMT2B gene (c.3014G>A; ClinVar #1333975) that was predicted to be deleterious, which likely contributed to dystonia (OMIM #617284) independently of DPD deficiency. In Subject 1, treatments with anti-epileptic therapies were insufficient for controlling seizures. The two subjects reported herein demonstrate the heterogeneity in clinical presentation associated with pediatric DPD deficiency. Further studies are needed to determine how loss of DPD function can negatively impact neurodevelopment in some individuals, while others who carry the same genetic variants are unaffected by the pediatric condition.
