Systems Biology
Comparative Proteomic Analysis of <em>Toxoplasma gondii</em> RH Wild-Type and Four SRS29B (SAG1) Knock-Out Clones Reveals Significant Differences between Individual Strains
Int J Mol Sci. 2023 Jun 21;24(13):10454. doi: 10.3390/ijms241310454.
ABSTRACT
In T. gondii, as well as in other model organisms, gene knock-out using CRISPR-Cas9 is a suitable tool to identify the role of specific genes. The general consensus implies that only the gene of interest is affected by the knock-out. Is this really the case? In a previous study, we generated knock-out (KO) clones of TgRH88_077450 (SRS29B; SAG1) which differed in the numbers of the integrated dihydrofolate-reductase-thymidylate-synthase (MDHFR-TS) drug-selectable marker. Clones 18 and 33 had a single insertion of MDHFR-TS within SRS29B. Clone 6 was disrupted by the insertion of a short unrelated DNA-sequence, but the marker was integrated elsewhere. In clone 30, the marker was inserted into SRS29B, and several other MDHFR-TS copies were found in the genome. KO and wild-type (WT) tachyzoites had similar shapes, dimensions, and vitality. This prompted us to investigate the impact of genetic engineering on the overall proteome patterns of the four clones as compared to the respective WT. Comparative shotgun proteomics of the five strains was performed. Overall, 3236 proteins were identified. Principal component analysis of the proteomes revealed five distinct clusters corresponding to the five strains by both iTop3 and iLFQ algorithms. Detailed analysis of the differentially expressed proteins revealed that the target of the KO, srs29B, was lacking in all KO clones. In addition to this protein, 20 other proteins were differentially expressed between KO clones and WT or between different KO clones. The protein exhibiting the highest variation between the five strains was srs36D encoded by TgRH_016110. The deregulated expression of SRS36D was further validated by quantitative PCR. Moreover, the transcript levels of three other selected SRS genes, namely SRS36B, SRS46, and SRS57, exhibited significant differences between individual strains. These results indicate that knocking out a given gene may affect the expression of other genes. Therefore, care must be taken when specific phenotypes are regarded as a direct consequence of the KO of a given gene.
PMID:37445632 | DOI:10.3390/ijms241310454
Clinical Network Systems Biology: Traversing the Cancer Multiverse
J Clin Med. 2023 Jul 7;12(13):4535. doi: 10.3390/jcm12134535.
ABSTRACT
In recent decades, cancer biology and medicine have ushered in a new age of precision medicine through high-throughput approaches that led to the development of novel targeted therapies and immunotherapies for different cancers. The availability of multifaceted high-throughput omics data has revealed that cancer, beyond its genomic heterogeneity, is a complex system of microenvironments, sub-clonal tumor populations, and a variety of other cell types that impinge on the genetic and non-genetic mechanisms underlying the disease. Thus, a systems approach to cancer biology has become instrumental in identifying the key components of tumor initiation, progression, and the eventual emergence of drug resistance. Through the union of clinical medicine and basic sciences, there has been a revolution in the development and approval of cancer therapeutic drug options including tyrosine kinase inhibitors, antibody-drug conjugates, and immunotherapy. This 'Team Medicine' approach within the cancer systems biology framework can be further improved upon through the development of high-throughput clinical trial models that utilize machine learning models, rapid sample processing to grow patient tumor cell cultures, test multiple therapeutic options and assign appropriate therapy to individual patients quickly and efficiently. The integration of systems biology into the clinical network would allow for rapid advances in personalized medicine that are often hindered by a lack of drug development and drug testing.
PMID:37445570 | DOI:10.3390/jcm12134535
MIRACUM-Pipe: An Adaptable Pipeline for Next-Generation Sequencing Analysis, Reporting, and Visualization for Clinical Decision Making
Cancers (Basel). 2023 Jul 1;15(13):3456. doi: 10.3390/cancers15133456.
ABSTRACT
(1) Background: Next-generation sequencing (NGS) of patients with advanced tumors is becoming an established method in Molecular Tumor Boards. However, somatic variant detection, interpretation, and report generation, require in-depth knowledge of both bioinformatics and oncology. (2) Methods: MIRACUM-Pipe combines many individual tools into a seamless workflow for comprehensive analyses and annotation of NGS data including quality control, alignment, variant calling, copy number variation estimation, evaluation of complex biomarkers, and RNA fusion detection. (3) Results: MIRACUM-Pipe offers an easy-to-use, one-prompt standardized solution to analyze NGS data, including quality control, variant calling, copy number estimation, annotation, visualization, and report generation. (4) Conclusions: MIRACUM-Pipe, a versatile pipeline for NGS, can be customized according to bioinformatics and clinical needs and to support clinical decision-making with visual processing and interactive reporting.
PMID:37444566 | DOI:10.3390/cancers15133456
Molecular Characterization of Esophageal Squamous Cell Carcinoma Using Quantitative Proteomics
Cancers (Basel). 2023 Jun 23;15(13):3302. doi: 10.3390/cancers15133302.
ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is a heterogeneous cancer associated with a poor prognosis in advanced stages. In India, it is the sixth most common cause of cancer-related mortality. In this study, we employed high-resolution mass spectrometry-based quantitative proteomics to characterize the differential protein expression pattern associated with ESCC. We identified several differentially expressed proteins including PDPN, TOP2A, POSTN and MMP2 that were overexpressed in ESCC. In addition, we identified downregulation of esophagus tissue-enriched proteins such as SLURP1, PADI1, CSTA, small proline-rich proteins such as SPRR3, SPRR2A, SPRR1A, KRT4, and KRT13, involved in squamous cell differentiation. We identified several overexpressed proteins mapped to the 3q24-29 chromosomal region, aligning with CNV alterations in this region reported in several published studies. Among these, we identified overexpression of SOX2, TP63, IGF2BP2 and RNF13 that are encoded by genes in the 3q26 region. Functional enrichment analysis revealed proteins involved in cell cycle pathways, DNA replication, spliceosome, and DNA repair pathways. We identified the overexpression of multiple proteins that play a major role in alleviating ER stress, including SYVN1 and SEL1L. The SYVN1/SEL1L complex is an essential part of the ER quality control machinery clearing misfolded proteins from the ER. SYVN1 is an E3 ubiquitin ligase that ubiquitinates ER-resident proteins. Interestingly, there are also other non-canonical substrates of SYVN1 which are known to play a crucial role in tumor progression. Thus, SYVN1 could be a potential therapeutic target in ESCC.
PMID:37444412 | DOI:10.3390/cancers15133302
Not Just a Banana: The Extent of Fruit Cross-Reactivity and Reaction Severity in Adults with Banana Allergy
Foods. 2023 Jun 23;12(13):2456. doi: 10.3390/foods12132456.
ABSTRACT
This cross-sectional study aimed to investigate the prevalence and clinical characteristics of cross-reactivity and co-allergy to other plant foods among adult patients with IgE-mediated banana allergy in Thailand. A structured questionnaire was used to assess clinical reactivity, and cross-reactivity diagnoses were based on reactions occurring within 2 years of banana allergy onset, within 3 h of intake, and confirmed by allergists. Among the 133 participants, the most commonly associated plant foods with clinical reactions were kiwi (83.5%), avocado (71.1%), persimmon (58.8%), grapes (44.0%), and durian (43.6%). Notably, 26.5% of the reported reactions to other plant foods were classified as severe. These findings highlight the common occurrence of cross-reactivity/co-allergy to other plant foods in banana-allergic patients, with a significant proportion experiencing severe reactions. Travelers to tropical regions should be aware of this risk and advised to avoid specific banana cultivars and plant foods with reported high cross-reactivity. The inclusion of self-injectable epinephrine in the management plan for patients with primary banana allergy should be considered due to the substantial proportion of reported severe reactions and the wide range of clinical cross-reactivity and co-allergy observed.
PMID:37444194 | DOI:10.3390/foods12132456
Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach
Int J Environ Res Public Health. 2023 Jul 3;20(13):6288. doi: 10.3390/ijerph20136288.
ABSTRACT
Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.
PMID:37444135 | DOI:10.3390/ijerph20136288
A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions
Cells. 2023 Jul 6;12(13):1795. doi: 10.3390/cells12131795.
ABSTRACT
Glomerular disease due to podocyte malfunction is a major factor in the pathogenesis of chronic kidney disease. Identification of podocyte-specific signaling pathways is therefore a prerequisite to characterizing relevant disease pathways and developing novel treatment approaches. Here, we employed loss of function studies for EPB41L5 (Yurt) as a central podocyte gene to generate a cell type-specific disease model. Loss of Yurt in fly nephrocytes caused protein uptake and slit diaphragm defects. Transcriptomic and proteomic analysis of human EPB41L5 knockout podocytes demonstrated impaired mechanotransduction via the YAP/TAZ signaling pathway. Further analysis of specific inhibition of the YAP/TAZ-TEAD transcription factor complex by TEADi led to the identification of ARGHAP29 as an EPB41L5 and YAP/TAZ-dependently expressed podocyte RhoGAP. Knockdown of ARHGAP29 caused increased RhoA activation, defective lamellipodia formation, and increased maturation of integrin adhesion complexes, explaining similar phenotypes caused by loss of EPB41L5 and TEADi expression in podocytes. Detection of increased levels of ARHGAP29 in early disease stages of human glomerular disease implies a novel negative feedback loop for mechanotransductive RhoA-YAP/TAZ signaling in podocyte physiology and disease.
PMID:37443829 | DOI:10.3390/cells12131795
Microvesicle-Mediated Tissue Regeneration Mitigates the Effects of Cellular Ageing
Cells. 2023 Jun 23;12(13):1707. doi: 10.3390/cells12131707.
ABSTRACT
Extracellular vesicles (EVs), comprising microvesicles (MVs) and exosomes (Exos), are membranous vesicles secreted by cells which mediate the repair of cellular and tissue damage via paracrine mechanisms. The action of EVs under normative and morbid conditions in the context of ageing remains largely unexplored. We demonstrate that MVs, but not Exos, from Pathfinder cells (PCs), a putative stem cell regulatory cell type, enhance the repair of human dermal fibroblast (HDF) and mesenchymal stem cell (MSC) co-cultures, following both mechanical and genotoxic stress. Critically, this effect was found to be both cellular age and stress specific. Notably, MV treatment was unable to repair mechanical injury in older co-cultures but remained therapeutic following genotoxic stress. These observations were further confirmed in human dermal fibroblast (HDF) and vascular smooth muscle cell (VSMC) co-cultures of increasing cellular age. In a model of comorbidity comprising co-cultures of HDFs and highly senescent abdominal aortic aneurysm (AAA) VSMCs, MV administration appeared to be senotherapeutic, following both mechanical and genotoxic stress. Our data provide insights into EVs and the specific roles they play during tissue repair and ageing. These data will potentiate the development of novel cell-free therapeutic interventions capable of attenuating age-associated morbidities and avoiding undesired effects.
PMID:37443741 | DOI:10.3390/cells12131707
The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets
Nat Cell Biol. 2023 Jul 13. doi: 10.1038/s41556-023-01178-w. Online ahead of print.
ABSTRACT
Lipid droplets (LDs) are crucial organelles for energy storage and lipid homeostasis. Autophagy of LDs is an important pathway for their catabolism, but the molecular mechanisms mediating LD degradation by selective autophagy (lipophagy) are unknown. Here we identify spartin as a receptor localizing to LDs and interacting with core autophagy machinery, and we show that spartin is required to deliver LDs to lysosomes for triglyceride mobilization. Mutations in SPART (encoding spartin) lead to Troyer syndrome, a form of complex hereditary spastic paraplegia1. Interfering with spartin function in cultured human neurons or murine brain neurons leads to LD and triglyceride accumulation. Our identification of spartin as a lipophagy receptor, thus, suggests that impaired LD turnover contributes to Troyer syndrome development.
PMID:37443287 | DOI:10.1038/s41556-023-01178-w
Challenges of implementing computer-aided diagnostic models for neuroimages in a clinical setting
NPJ Digit Med. 2023 Jul 13;6(1):129. doi: 10.1038/s41746-023-00868-x.
ABSTRACT
Advances in artificial intelligence have cultivated a strong interest in developing and validating the clinical utilities of computer-aided diagnostic models. Machine learning for diagnostic neuroimaging has often been applied to detect psychological and neurological disorders, typically on small-scale datasets or data collected in a research setting. With the collection and collation of an ever-growing number of public datasets that researchers can freely access, much work has been done in adapting machine learning models to classify these neuroimages by diseases such as Alzheimer's, ADHD, autism, bipolar disorder, and so on. These studies often come with the promise of being implemented clinically, but despite intense interest in this topic in the laboratory, limited progress has been made in clinical implementation. In this review, we analyze challenges specific to the clinical implementation of diagnostic AI models for neuroimaging data, looking at the differences between laboratory and clinical settings, the inherent limitations of diagnostic AI, and the different incentives and skill sets between research institutions, technology companies, and hospitals. These complexities need to be recognized in the translation of diagnostic AI for neuroimaging from the laboratory to the clinic.
PMID:37443276 | DOI:10.1038/s41746-023-00868-x
Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases
Nat Genet. 2023 Jul 13. doi: 10.1038/s41588-023-01443-6. Online ahead of print.
ABSTRACT
Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene-trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene-trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox.
PMID:37443254 | DOI:10.1038/s41588-023-01443-6
Structural journey of an insecticidal protein against western corn rootworm
Nat Commun. 2023 Jul 13;14(1):4171. doi: 10.1038/s41467-023-39891-7.
ABSTRACT
The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly.
PMID:37443175 | DOI:10.1038/s41467-023-39891-7
Functional decomposition of metabolism allows a system-level quantification of fluxes and protein allocation towards specific metabolic functions
Nat Commun. 2023 Jul 13;14(1):4161. doi: 10.1038/s41467-023-39724-7.
ABSTRACT
Quantifying the contribution of individual molecular components to complex cellular processes is a grand challenge in systems biology. Here we establish a general theoretical framework (Functional Decomposition of Metabolism, FDM) to quantify the contribution of every metabolic reaction to metabolic functions, e.g. the synthesis of biomass building blocks. FDM allowed for a detailed quantification of the energy and biosynthesis budget for growing Escherichia coli cells. Surprisingly, the ATP generated during the biosynthesis of building blocks from glucose almost balances the demand from protein synthesis, the largest energy expenditure known for growing cells. This leaves the bulk of the energy generated by fermentation and respiration unaccounted for, thus challenging the common notion that energy is a key growth-limiting resource. Moreover, FDM together with proteomics enables the quantification of enzymes contributing towards each metabolic function, allowing for a first-principle formulation of a coarse-grained model of global protein allocation based on the structure of the metabolic network.
PMID:37443156 | DOI:10.1038/s41467-023-39724-7
Antimicrobial properties of green synthesized novel TiO<sub>2</sub> nanoparticles using Iranian propolis extracts
J Basic Microbiol. 2023 Jul 13. doi: 10.1002/jobm.202300221. Online ahead of print.
ABSTRACT
The oral antimicrobial and cytotoxic properties of green synthesized novel titanium dioxide nanoparticles (TiO2 NPs) using Iranian propolis extracts were investigated on oral bacteria and fibroblast cells. In this study, propolis was sampled, and alcoholic extracts were prepared. The TiO2 NPs were biosynthesized using propolis extracts. The synthesized TiO2 NPs were characterized by scanning electron microscope (SEM), X-ray diffraction analysis, energy-dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering, ultraviolet-visible (UV-Vis), transmission electron microscope, Brunauer-Emmett-Teller, and zeta potential. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), minimal inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, biofilm formation, and degradation tests were studied to clarify the oral antimicrobial properties of green synthesized TiO2 NPs. According to the FTIR analysis, the propolis extract contained flavonoids and phenolic compounds in addition to TiO2 NPs. Additionally, UV-Vis revealed that intense bands had formed NPs. EDX spectra and SEM images revealed that the stabilizing agent was in perfect quasi-spherical shapes around 21 nm. An EDX spectrum was used to verify the presence of titanium and oxygen. There were no significant cytotoxicity effects. The antibacterial results showed that Pro1TiO2 (Khalkhal sample) had better effects than Pro2TiO2 (Gilan sample) and TiO2 NPs. The present study presents a new process for synthesizing TiO2 NPs from propolis extracts with less toxic effects and user-friendly, eco-friendly, and economical materials. Pro1TiO2 NPs may be considered the best candidate for clinical application.
PMID:37442766 | DOI:10.1002/jobm.202300221
Minimizing enzyme mass to decompose flux distribution for identifying biologically relevant elementary flux modes
Biosystems. 2023 Jul 11:104981. doi: 10.1016/j.biosystems.2023.104981. Online ahead of print.
ABSTRACT
The flux distribution in metabolic network can be decomposed as non-negative linear combinations of elementary flux modes (EFMs). Identifying biologically relevant EFM combination by decomposing flux distribution in metabolic network is a useful method to study metabolisms in systems biology. However, the occurrence of biologically irrelevant EFMs hinders the application of such methods. In this paper, we introduce a novel method for identifying EFM combination by minimizing enzyme mass. Our proposed method, called EMMD (Enzyme Mass Minimization Decomposition), takes into consideration both thermodynamic and enzymatic constraints in stoichiometry metabolic models. By implementing EMMD, we can decompose the flux distributions in metabolic network to detect biologically relevant EFM combinations. We demonstrate the effectiveness of our method by applying it to the core Escherichia coli metabolic network and show that the optimal EFM combinations identified by EMMD are unique. Moreover, the optimal EFM combination identified by EMMD not only aligns more closely with experimental values in terms of estimated growth rate, but it also demonstrates more favorable thermodynamics. Finally, we investigated the growth of the core Escherichia coli metabolic network in Luria-Bertani medium containing different carbon sources, revealing the impact of various carbon sources on the growth rate of flux distribution. EMMD thus could be a promising complement to the existing flux decomposition tools.
PMID:37442363 | DOI:10.1016/j.biosystems.2023.104981
Coarse graining the human gut microbiome
Cell Host Microbe. 2023 Jul 12;31(7):1076-1078. doi: 10.1016/j.chom.2023.06.001.
ABSTRACT
The composition of the human gut microbiome is heterogeneous across people. However, if you squint, co-abundant microbial genera emerge, accounting for much of this ecological variability. In this issue of Cell Host & Microbe, Frioux et al. provide a workflow for identifying these bacterial guilds, or "enterosignatures."
PMID:37442093 | DOI:10.1016/j.chom.2023.06.001
Mechanistic insights into hormesis induced by erythromycin in the marine alga Thalassiosira weissflogii
Ecotoxicol Environ Saf. 2023 Jul 11;263:115242. doi: 10.1016/j.ecoenv.2023.115242. Online ahead of print.
ABSTRACT
Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.
PMID:37441949 | DOI:10.1016/j.ecoenv.2023.115242
AMBAR - Interactive Alteration annotations for molecular tumor boards
Comput Methods Programs Biomed. 2023 Jul 6;240:107697. doi: 10.1016/j.cmpb.2023.107697. Online ahead of print.
ABSTRACT
MOTIVATION: Personalized decision-making for cancer therapy relies on molecular profiling from sequencing data in combination with database evidence and expert knowledge. Molecular tumor boards (MTBs) bring together clinicians and scientists with diverse expertise and are increasingly established in the clinical routine for therapeutic interventions. However, the analysis and documentation of patients data are still time-consuming and difficult to manage for MTBs, especially as few tools are available for the amount of information required.
RESULTS: To overcome these limitations, we developed an interactive web application AMBAR (Alteration annotations for Molecular tumor BoARds), for therapeutic decision-making support in MTBs. AMBAR is an R shiny-based application that allows customization, interactive filtering, visualization, adding expert knowledge, and export to clinical systems of annotated mutations.
AVAILABILITY: AMBAR is dockerized, open source and available at https://sysbio.uni-ulm.de/?Software:Ambar Contact:hans.kestler@uni-ulm.de.
PMID:37441893 | DOI:10.1016/j.cmpb.2023.107697
Concepts, mechanisms and implications of long-term epigenetic inheritance
Curr Opin Genet Dev. 2023 Jul 11;81:102087. doi: 10.1016/j.gde.2023.102087. Online ahead of print.
ABSTRACT
Many modes and mechanisms of epigenetic inheritance have been elucidated in eukaryotes. Most of them are relatively short-term, generally not exceeding one or a few organismal generations. However, emerging evidence indicates that one mechanism, cytosine DNA methylation, can mediate epigenetic inheritance over much longer timescales, which are mostly or completely inaccessible in the laboratory. Here we discuss the evidence for, and mechanisms and implications of, such long-term epigenetic inheritance. We argue that compelling evidence supports the long-term epigenetic inheritance of gene body methylation, at least in the model angiosperm Arabidopsis thaliana, and that variation in such methylation can therefore serve as an epigenetic basis for phenotypic variation in natural populations.
PMID:37441873 | DOI:10.1016/j.gde.2023.102087
The impact of amine and carboxyl functionalised microplastics on the physiology of daphnids
J Hazard Mater. 2023 Jul 10;458:132023. doi: 10.1016/j.jhazmat.2023.132023. Online ahead of print.
ABSTRACT
Plastic waste is considered a major threat for terrestrial, marine and freshwater ecosystems. Ingestion of primary or secondary microparticles resulting from plastic degradation can lead to their trophic transfer raising serious health concerns. In this study, the effect of amine and carboxy functionalized polystyrene microparticles on the physiology of daphnids was investigated with a combination of phenotypic and metabolic endpoints. Carboxy functionalized microparticles showed higher toxicity in acute exposures compared to their amine counterparts. Accumulation of both microparticles in animal gut was confirmed by stereo-microscopy as well as fluorescent microscopy which showed no presence of particles in the rest of the animal. Fluorescence based quantification of microparticles extracted from animal lysates validated their concentration-dependent uptake. Additionally, exposure of daphnids to amine and carboxy functionalized microparticles resulted in increased activities of key enzymes related to metabolism and detoxification. Finally, significant metabolic perturbations were discovered following exposure to microplastics. These findings suggest that polystyrene microparticles can hinder organism performance of the freshwater species and highlight the importance of seeking for holistic and physiological endpoints for pollution assessment.
PMID:37441864 | DOI:10.1016/j.jhazmat.2023.132023