Systems Biology

Native nucleosomes intrinsically encode genome organization principles

Wed, 2025-05-07 06:00

Nature. 2025 May 7. doi: 10.1038/s41586-025-08971-7. Online ahead of print.

ABSTRACT

The eukaryotic genome is packed into nucleosomes of 147 base pairs around a histone core and is organized into euchromatin and heterochromatin, corresponding to the A and B compartments, respectively1,2. Here we investigated whether individual nucleosomes contain sufficient information for 3D genomic organization into compartments, for example, in their biophysical properties. We purified native mononucleosomes to high monodispersity and used physiological concentrations of polyamines to determine their condensability. The chromosomal regions known to partition into A compartments have low condensability and those for B compartments have high condensability. Chromatin polymer simulations using condensability as the only input, without any trans factors, reproduced the A/B compartments. Condensability is also strongly anticorrelated with gene expression, particularly near the promoters and in a cell type-dependent manner. Therefore, mononucleosomes have biophysical properties associated with genes being on or off. Comparisons with genetic and epigenetic features indicate that nucleosome condensability is an emergent property, providing a natural axis on which to project the high-dimensional cellular chromatin state. Analysis using various condensing agents or histone modifications and mutations indicates that the genome organization principle encoded into nucleosomes is mostly electrostatic in nature. Polyamine depletion in mouse T cells, resulting from either knocking out or inhibiting ornithine decarboxylase, results in hyperpolarized condensability, indicating that when cells cannot rely on polyamines to translate the biophysical properties of nucleosomes to 3D genome organization, they accentuate condensability contrast, which may explain the dysfunction observed with polyamine deficiency3-5.

PMID:40335690 | DOI:10.1038/s41586-025-08971-7

Categories: Literature Watch

Potential shared neoantigens from pan-cancer transcript isoforms

Wed, 2025-05-07 06:00

Sci Rep. 2025 May 7;15(1):15886. doi: 10.1038/s41598-025-00817-6.

ABSTRACT

Isoform switching in cancer is a prevalent phenomenon with significant implications for immunotherapy, as actionable neoantigens derived from these cancer-specific events would be applicable to broad categories of patients, reducing the necessity for personalized treatments. By integrating five large-scale transcriptomic datasets comprising over 19,500 samples across 29 cancer and 54 normal tissue types, we identified cancer-associated isoform switching events common to multiple cancer types, several of which involve genes with established mechanistic roles in oncogenesis. The presence of neoantigen-containing peptides derived from these transcripts was confirmed in broad cancer and normal tissue proteome datasets and the binding affinity of predicted neoantigens to the human leukocyte antigen (HLA) complex via molecular dynamics simulations. The study presents strong evidence that isoform switching in cancer is a significant source of actionable neoantigens that have the capability to trigger an immune response. These findings suggest that isoform switching events could potentially be leveraged for broad immunotherapeutic strategies across various cancer types.

PMID:40335513 | DOI:10.1038/s41598-025-00817-6

Categories: Literature Watch

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction

Wed, 2025-05-07 06:00

Nat Commun. 2025 May 7;16(1):4260. doi: 10.1038/s41467-025-59525-4.

ABSTRACT

Blood cell phenotypes are routinely tested in healthcare to inform clinical decisions. Genetic variants influencing mean blood cell phenotypes have been used to understand disease aetiology and improve prediction; however, additional information may be captured by genetic effects on observed variance. Here, we mapped variance quantitative trait loci (vQTL), i.e. genetic loci associated with trait variance, for 29 blood cell phenotypes from the UK Biobank (N ~ 408,111). We discovered 176 independent blood cell vQTLs, of which 147 were not found by additive QTL mapping. vQTLs displayed on average 1.8-fold stronger negative selection than additive QTL, highlighting that selection acts to reduce extreme blood cell phenotypes. Variance polygenic scores (vPGSs) were constructed to stratify individuals in the INTERVAL cohort (N ~ 40,466), where the genetically most variable individuals had increased conventional PGS accuracy (by ~19%) relative to the genetically least variable individuals. Genetic prediction of blood cell traits improved by ~10% on average combining PGS with vPGS. Using Mendelian randomisation and vPGS association analyses, we found that alcohol consumption significantly increased blood cell trait variances highlighting the utility of blood cell vQTLs and vPGSs to provide novel insight into phenotype aetiology as well as improve prediction.

PMID:40335489 | DOI:10.1038/s41467-025-59525-4

Categories: Literature Watch

Intelligent biomanufacturing of water-soluble vitamins

Wed, 2025-05-07 06:00

Trends Biotechnol. 2025 May 6:S0167-7799(25)00134-9. doi: 10.1016/j.tibtech.2025.04.007. Online ahead of print.

ABSTRACT

Given the crucial role of water-soluble vitamins in the human body and the rising demand for natural sources, their biosynthesis has gained the attention of researchers. This review offers a comprehensive look at recent progress in water-soluble vitamin biosynthesis, emphasizing synthetic biotechnology for green biomanufacturing. Specifically, it encompasses the optimization of biological components, pathways, and systems, as well as energy metabolism regulation, stress-tolerance enhancement, high-throughput screening, and the upscaling of production processes. It also envisages intelligent biomanufacturing platforms, highlighting the role of systems biology and artificial intelligence (AI), and proposes future research directions, such as integrating AI-driven metabolic models, enzyme engineering, and cell-free systems, to address limitations in the efficiency, toxicity, and scalability of water-soluble vitamin production.

PMID:40335344 | DOI:10.1016/j.tibtech.2025.04.007

Categories: Literature Watch

Chlorogenic acid simultaneously enhances the oxidative protection and anti-digestibility of porous starch

Wed, 2025-05-07 06:00

Int J Biol Macromol. 2025 May 5:143949. doi: 10.1016/j.ijbiomac.2025.143949. Online ahead of print.

ABSTRACT

Porous starch (PS) has been utilized as an oral protective carrier to enhance the oxidative stability of liposoluble nutrients. However, PS releases more glucose during digestion, thereby increasing the risk of chronic diseases. Chlorogenic acid (CA) has excellent antioxidant properties and enhances the starch digestion resistance. To simultaneously enhance the oxidative protection and anti-digestibility, PS was blended with CA. Morphological analysis revealed that PSs with pores absorbed liposoluble substances. Surface area, total pore volume, and oxidative stability analyses demonstrated that rice starch (RS) enzymatically hydrolyzed for 12 h (PS12) loaded more substances and exerted a better protective effect in cooperation with CA. Simulated digestion confirmed that PS12-CA1 had the best anti-digestibility among PS12-CAs and a similar digestibility as RS. Additionally, CA treatment resulted in more anti-digestive V-type crystals in PSs, which resisted digestion. This study showed that the combination of PS and CA simultaneously enhanced oxidative protection and reduced the digestibility of PS. Thus, CA treatment makes PS a better oral nutrient delivery.

PMID:40334898 | DOI:10.1016/j.ijbiomac.2025.143949

Categories: Literature Watch

Microbiome catalog and dynamics of the Chinese liquor fermentation process

Wed, 2025-05-07 06:00

Bioresour Technol. 2025 May 5:132620. doi: 10.1016/j.biortech.2025.132620. Online ahead of print.

ABSTRACT

Fermented food remains poorly understood, largely due to the lack of knowledge about microbes in food fermentation. Here, this study constructed Moutai Fermented Grain Catalog (MTFGC), a representative liquor fermented by one of the most complex fermentations. MTFGC comprised 8,379,551 non-redundant genes and 5,159 metagenome-assembled genomes, with 20% species and 20% genes being novel. Additionally, 25,625 biosynthetic gene clusters (BGCs) and 28 BGC-enriched species were identified. Moreover, the microbial community assembly was deterministic, with significant species and gene changes in early fermentation stages, while stabilizing in later stages. Further BGC-knockout experiments verified Bacillus licheniformis, a BGC-enriched species, employed its BGCs for synthesizing the aroma-related lipopeptide lichenysin. This study has established the largest genetic resource for fermented food, uncovering its uniqueness and high metabolic potential. These findings facilitate the transition potential from traditional fermentation to precision-driven synthetic biology in food systems.

PMID:40334798 | DOI:10.1016/j.biortech.2025.132620

Categories: Literature Watch

Lipoprotein (a) integrates monocyte-mediated thrombosis and inflammation in atherosclerotic cardiovascular disease

Wed, 2025-05-07 06:00

J Lipid Res. 2025 May 5:100820. doi: 10.1016/j.jlr.2025.100820. Online ahead of print.

ABSTRACT

BACKGROUND: Elevated levels of lipoprotein (a) [Lp(a)], an apolipoprotein B particle, are causally linked to atherosclerotic cardiovascular disease (ASCVD). Lp(a) is thought to promote ASCVD through multiple mechanisms, including its effects on cholesterol transport, inflammation, and thrombosis.

OBJECTIVE: Define the mechanisms that integrate Lp(a)-mediated cholesterol accumulation, inflammation, and thrombosis.

METHODS: In this study, we employed systems biology approaches, including proteomics, transcriptomics, and mass cytometry, to define the immune cellular and molecular phenotypes in ASCVD subjects with high and low Lp(a) levels and the molecular mechanisms through which Lp(a) mediates monocyte-driven inflammation and thrombosis.

RESULTS: In 64 stable ASCVD subjects (41 with high Lp(a) [median Lp(a) 228.7 nmol/L] and 23 with low Lp(a) [median Lp(a) 17.8 nmol/L]), we found that circulating markers of inflammation (CCL28, IL-17D) and vascular dysfunction (tissue factor [TF]; 6.4 vs 5.7 normalized protein expression (NPX); p=0.01) were elevated in subjects with high Lp(a) levels compared with those with low Lp(a) levels. Although total monocyte and hsCRP levels were similar between the groups, CD14+ monocytes from ASCVD subjects with an elevated Lp(a) were primed and expressed more TF at baseline and in response to stress. Mechanistically, we found that Lp(a) itself can activate monocytes through Toll-like receptor 2 (TLR2) and nuclear factor kappa B (NFκB) signaling, driving both the induction of TF and TF activity.

CONCLUSIONS: Overall, these studies are the first to link Lp(a) to monocyte-mediated inflammation and thrombosis. They demonstrate a novel mechanism through TLR2, NFκB, and monocyte TF by which Lp(a) amplifies immunothrombotic risk.

PMID:40334781 | DOI:10.1016/j.jlr.2025.100820

Categories: Literature Watch

Beyond CEN.PK - parallel engineering of selected S. cerevisiae strains reveals that superior chassis strains require different engineering approaches for limonene production

Wed, 2025-05-07 06:00

Metab Eng. 2025 May 5:S1096-7176(25)00075-8. doi: 10.1016/j.ymben.2025.04.011. Online ahead of print.

ABSTRACT

Genetically engineered microbes are increasingly utilized to produce a broad range of high-value compounds. However, most studies start with only a very narrow group of genetically tractable type strains that have not been selected for maximum titers or industrial robustness. In this study, we used high-throughput screening and parallel metabolic engineering to identify and optimize Saccharomyces cerevisiae chassis strains for the production of limonene, a monoterpene with applications in flavors, fragrances, and biofuels. We screened 921 genetically and phenotypically distinct S. cerevisiae strains for limonene tolerance and lipid content to identify optimal chassis strains for precision fermentation of limonene. In parallel, we also evaluated 16 different plant limonene synthases. Our results revealed that two of the selected strains showed approximately a 2-fold increase in titers compared to CEN.PK2-1C, the type strain that is often used as a chassis for limonene production, with the same genetic modifications in the mevalonate pathway. Intriguingly, the most effective engineering strategy proved strain-specific. Metabolic profiling revealed that this difference is likely explained by differences in native mevalonate production. Ultimately, by using strain-specific engineering strategies, we achieved 844 mg/L in a new strain, 40% higher than the titer (605 mg/L) achieved by CEN.PK2-1C. Our findings demonstrate the potential of leveraging genetic diversity in S. cerevisiae for monoterpene bioproduction and highlight the necessity for tailoring metabolic engineering strategies to specific strains.

PMID:40334774 | DOI:10.1016/j.ymben.2025.04.011

Categories: Literature Watch

Start, Stop, Resume and Proceed: ZmSSRP1 mediates the progression of RNA polymerase II and kernel development in maize

Wed, 2025-05-07 06:00

Plant Cell. 2025 May 7:koaf113. doi: 10.1093/plcell/koaf113. Online ahead of print.

NO ABSTRACT

PMID:40334133 | DOI:10.1093/plcell/koaf113

Categories: Literature Watch

The impact of mutations on TP53 protein and MicroRNA expression in HNSCC: Novel insights for diagnostic and therapeutic strategies

Wed, 2025-05-07 06:00

PLoS One. 2025 May 7;20(5):e0307859. doi: 10.1371/journal.pone.0307859. eCollection 2025.

ABSTRACT

The tumor suppressor protein p53 (TP53) is frequently mutated in various types of human malignancies, including HNSCC, which affects tumor growth, prognosis, and treatment. Gaining insight into the impact of TP53 mutations in HNSCC is crucial for developing new diagnostic and therapeutic methods. In this study, we aimed to investigate the influence of mutations on the structure and functions of the TP53 protein and miRNA expression using computational analysis. The genomic data of patients with HNSCC were obtained from TCGA, and the impact of mutations on the TP53 gene was investigated using different bioinformatics tools. Results: The findings showed that the TP53 mutations increased TP53 expression levels in HNSCC and were associated with a poor prognosis. Furthermore, hsa-mir-133b expression was reduced in TP53-mutated samples, significantly affecting patient survival in HNSCC. Six mutations, including R273C, G105C, G266E, Q136H/P, and R280G, were identified as deleterious, carcinogenic, driver, highly conserved, and exposed. These mutations were located in the P53 domain, and PTM analysis revealed that R280G and R273C are at a methylation site, and R273C, Q136H/P, and R280G are located in the protein pocket. The docking research indicated that these mutations decreased the binding affinity for DNA, with R273C, R280G, G266E, and G105C displaying the most significant differences. The molecular dynamics analysis indicates that R280G, Q136H, and G105C mutations confer a gain of function by stabilizing the TP53-substrate complex. Conclusions: Based on the research findings, the mutations on TP53 were found to have an impact on protein and miRNA expression, development, survival, and progression of HNSCC patients, and has-mir-133b could be a promising novel biomarker for monitoring the progression of HNSCC. It was discovered that G105C and Q136H/P, as novel mutations, affect the function and structure of proteins causing HNSCC, which indicates that they could be interesting subjects for further investigation, diagnostics, and therapeutic strategies. Furthermore, the precise positioning of R280G and R273C within the methylation site and Q136H/P in the binding site has been documented for the first time. Moreover, the G105C, Q136H, and R280G mutations that stabilized TP53 structure and altered its interaction dynamics with substrates may serve as novel potential diagnostic biomarkers in cancer, guiding patient stratification and personalized treatment strategies. The molecular dynamics analysis provides insights into how specific TP53 mutations impact protein structure, stability, and function upon substrate binding, highlighting their role in cancer biology and potential implications for therapeutic interventions. This paper provides a novel understanding of the mechanisms by which these mutations contribute to the development of cancer.

PMID:40333905 | DOI:10.1371/journal.pone.0307859

Categories: Literature Watch

The Frequency and Spread of a GABA-Gated Chloride Channel Target-Site Mutation and Its Impact on the Efficacy of Ethiprole Against Neotropical Brown Stink Bug, <em>Euschistus heros</em> (Hemiptera: Pentatomidae)

Wed, 2025-05-07 06:00

Insects. 2025 Apr 17;16(4):422. doi: 10.3390/insects16040422.

ABSTRACT

The Neotropical brown stink bug (NBSB), Euschistus heros, is the most prevalent sucking soybean pest in Brazil, and control of it largely relies on the application of synthetic insecticides such as ethiprole, a phenylpyrazole insecticide targeting GABA-gated chloride channels encoded by the Rdl (resistant to dieldrin) gene. This study monitored 41 NBSB populations collected between 2021 and 2024 and revealed, for the first time, the presence of a mutation, A301S, in NBSB RDL receptors commonly known to confer target-site resistance to channel blockers such as phenylpyrazoles. Laboratory contact bioassays with ethiprole at 150 g a.i./ha (ethiprole label dose) revealed that most populations were quite susceptible, despite rather high resistance allele frequencies in some populations. Genotyping results confirmed that susceptible and A301S heterozygous genotypes largely dominate in frequency compared to homozygous resistant individuals, which exhibited high survivorship (84%) when exposed to discriminating rates of ethiprole in laboratory bioassays, while susceptible and heterozygote individuals showed lower survival rates (13% and 34%, respectively), suggesting an incompletely recessive trait conferring ethiprole resistance. Furthermore, we developed a TaqMan assay for molecular genotyping to monitor the spread of resistance allele frequency and to inform resistance management strategies for sustainable NBSB control using highly effective phenylpyrazole insecticides such as ethiprole.

PMID:40332961 | DOI:10.3390/insects16040422

Categories: Literature Watch

Maral Root Extract and Its Main Constituent 20-Hydroxyecdysone Enhance Stress Resilience in <em>Caenorhabditis elegans</em>

Wed, 2025-05-07 06:00

Int J Mol Sci. 2025 Apr 15;26(8):3739. doi: 10.3390/ijms26083739.

ABSTRACT

As human life expectancy continues to rise, managing age-related diseases and preserving health in later years remain significant challenges. Consequently, there is a growing demand for strategies that enhance both the quality and the duration of life. Interventions that promote longevity, particularly those derived from natural sources, are popular for their potential to address age-related health concerns. Adaptogens-herbs, roots, and mushrooms-are valued in food science and nutrition for their ability to enhance resilience and overall well-being. Among these, Rhaponticum carthamoides (Willd.) Iljin, known as maral root (Russian leuzea), holds a prominent place in Siberian traditional medicine. The root extract, abundant in bioactive compounds such as flavonoids and phytoecdysteroids, is reputed for reducing fatigue, boosting strength, and offering immunomodulatory benefits. However, the effects of the plant extract on lifespan and age-related decline remains poorly studied. This study investigates the effect of maral root extract and phytoecdysteroids-ecdysterone, ponasterone, and turkesterone-on aging using Caenorhabditis elegans as a model organism. A sensitive liquid chromatography method with photodiode array detection was developed and validated to quantify the phytoecdysteroids in the extract. Behavioural and stress-response assays revealed that maral root not only extends lifespan but also significantly enhanced healthspan, stress resilience, and fitness in the nematodes. Additionally, treatment with ecdysterone, the most abundant compound in the root extract, improved healthspan by enhancing stress response. These findings underscore the potential of maral root as a natural adaptogen to mitigate age-related decline, providing valuable insights into natural longevity interventions.

PMID:40332350 | DOI:10.3390/ijms26083739

Categories: Literature Watch

Molecular Mechanisms of Virulence Regulation in <em>Staphylococcus aureus</em>: A Journey into Reconstitutive Biochemistry

Wed, 2025-05-07 06:00

Acc Chem Res. 2025 May 7. doi: 10.1021/acs.accounts.5c00117. Online ahead of print.

ABSTRACT

ConspectusMethodological development in the fields of genetics, chemical biology, and biochemistry over the last several decades has provided researchers with a diverse set of powerful tools to investigate biological processes. Leveraging these innovations in concert, scientists can now characterize biological pathways at a level of complexity ranging from systems biology down to molecular and atomic detail.Throughout this Account, we illustrate how discoveries made using these tools build on each other to develop a comprehensive understanding of biological pathways. Advancements in genetic sequencing facilitates association of genotypes and phenotypes, independent of biochemical mechanism. Through the biochemical reconstitution of the interactions between biological macromolecules─including the small molecules (ligands and metabolites) and proteins─that participate in these biological pathways, scientists can characterize the specific molecular features that link genotype and phenotype. This facilitates identification of targets within these pathways that can be manipulated to achieve a greater understanding of the biological process or to develop interventions to improve human health outcomes.Specifically, we describe how this toolbox was leveraged to discover and characterize the molecular biochemistry underlying control of pathogenicity in the Gram-positive bacterium Staphylococcus aureus. Concurrent with advancements in the investigative tools available to the scientific community, we and others reported on the genetic, molecular, and biochemical/biophysical components of this regulatory system. Virulence control in S. aureus is achieved through a chemical system of bacterial cell-to-cell communication indexed to local population density, referred to as quorum sensing (QS). We and our collaborators identified that this QS system is encoded in the accessory gene regulator (agr) operon and functions via the biosynthesis, secretion, and accumulation of a short peptide signaling molecule─the autoinducing peptide (AIP)─in the local environment correlated with the growth of S. aureus in the same biological niche. Above a threshold concentration, these AIPs bind and activate a cell-surface receptor to stimulate an intracellular response resulting in altered gene expression and bacterial group behaviors. We discovered that chemical modification of these AIPs often generates molecules that exhibit potent inhibition of agr QS, with demonstrated therapeutic potential to treat S. aureus infections. We went on to characterize the biochemical mechanism of signaling molecule biosynthesis and receptor activation in controlled systems through in vitro reconstitution of the constituent enzymes and substrates. Biochemical reconstitution enabled quantitative assessment of biophysical parameters. These efforts culminated in the comprehensive characterization and functional in vitro reconstitution of agr QS in a synthetic system in a minimal model at the interface of genotype, mechanism, and phenotype.

PMID:40331756 | DOI:10.1021/acs.accounts.5c00117

Categories: Literature Watch

CAMI Benchmarking Portal: online evaluation and ranking of metagenomic software

Wed, 2025-05-07 06:00

Nucleic Acids Res. 2025 May 7:gkaf369. doi: 10.1093/nar/gkaf369. Online ahead of print.

ABSTRACT

Finding appropriate software and parameter settings to process shotgun metagenome data is essential for meaningful metagenomic analyses. To enable objective and comprehensive benchmarking of metagenomic software, the community-led initiative for the Critical Assessment of Metagenome Interpretation (CAMI) promotes standards and best practices. Since 2015, CAMI has provided comprehensive datasets, benchmarking guidelines, and challenges. However, benchmarking had to be conducted offline, requiring substantial time and technical expertise and leading to gaps in results between challenges. We introduce the CAMI Benchmarking Portal-a central repository of CAMI resources and web server for the evaluation and ranking of metagenome assembly, binning, and taxonomic profiling software. The portal simplifies evaluation, enabling users to easily compare their results with previous and other users' submissions through a variety of metrics and visualizations. As a demonstration, we benchmark software performance on the marine dataset of the CAMI II challenge. The portal currently hosts 28 675 results and is freely available at https://cami-challenge.org/.

PMID:40331433 | DOI:10.1093/nar/gkaf369

Categories: Literature Watch

The CpG Landscape of Protein Coding DNA in Vertebrates

Wed, 2025-05-07 06:00

Evol Appl. 2025 May 4;18(5):e70101. doi: 10.1111/eva.70101. eCollection 2025 May.

ABSTRACT

DNA methylation has fundamental implications for vertebrate genome evolution by influencing the mutational landscape, particularly at CpG dinucleotides. Methylation-induced mutations drive a genome-wide depletion of CpG sites, creating a dinucleotide composition bias across the genome. Examination of the standard genetic code reveals CpG to be the only facultative dinucleotide; it is however unclear what specific implications CpG bias has on protein coding DNA. Here, we use theoretical considerations of the genetic code combined with empirical genome-wide analyses in six vertebrate species-human, mouse, chicken, great tit, frog, and stickleback-to investigate how CpG content is shaped and maintained in protein-coding genes. We show that protein-coding sequences consistently exhibit significantly higher CpG content than noncoding regions and demonstrate that CpG sites are enriched in genes involved in regulatory functions and stress responses, suggesting selective maintenance of CpG content in specific loci. These findings have important implications for evolutionary applications in both natural and managed populations: CpG content could serve as a genetic marker for assessing adaptive potential, while the identification of CpG-free codons provides a framework for genome optimization in breeding and synthetic biology. Our results underscore the intricate interplay between mutational biases, selection, and epigenetic regulation, offering new insights into how vertebrate genomes evolve under varying ecological and selective pressures.

PMID:40330995 | PMC:PMC12050414 | DOI:10.1111/eva.70101

Categories: Literature Watch

Case Report: Fatal case of dual infection <em>Metapneumovirus</em> complicated by <em>Streptococcus pyogenes</em>

Wed, 2025-05-07 06:00

Front Med (Lausanne). 2025 Apr 22;12:1576583. doi: 10.3389/fmed.2025.1576583. eCollection 2025.

ABSTRACT

Human Metapneumovirus (hMPV) is a common cause of acute respiratory viral infection in humans, typically occurring in children and causing no serious complications. However, the severity of the disease can be exacerbated by certain bacterial pathogens that lead to severe illness and even death. This report details a fulminant case of dual infection with hMPV and group A Streptococcus (Streptococcus pyogenes) in a three-year-old child. The whole genome sequencing of isolated clinical S. pyogenes strains was conducted, followed by an analysis of the genomic characteristics of the pathogen. Also, potential viral and bacterial pathogens were identified by qPCR and 16S rRNA metagenomic sequencing in any autopsy materials obtained from the patient. Children who had contact with the patient and began to exhibit symptoms of a cold were also tested and confirmed to have uncomplicated hMPV infection. The S. pyogenes strain has been found to contain five genes for various streptococcal exotoxins (speA, speB, speJ, speG and smeZ). In addition, the speA gene is situated in close proximity to the prophage, which may suggest that it is encoded and transferred specifically by the bacteriophage. We hypothesize that it was the cumulative effects of different streptococcal exotoxins that led to the patient's death.

PMID:40330784 | PMC:PMC12052555 | DOI:10.3389/fmed.2025.1576583

Categories: Literature Watch

SAPID: A Strategy to Analyze Plant Extracts Taste In Depth. Application to the complex taste of <em>Swertia chirayita</em> (Roxb.) H.Karst

Wed, 2025-05-07 06:00

Curr Res Food Sci. 2025 Apr 5;10:101043. doi: 10.1016/j.crfs.2025.101043. eCollection 2025.

ABSTRACT

Analyzing bitterness is challenging because of the diverse range of bitter compounds, the variability in sensory perception, and its complex interaction with other tastes. To address this, we developed an untargeted approach to deconvolute the taste and molecular composition of complex plant extracts. We applied our methodology to an ethanolic extract of Swertia chirayita (Roxb.) H.Karst., a plant recognized for its distinctive bitterness. Chemical characterization was performed through nuclear magnetic resonance spectroscopy experiments together with untargeted liquid chromatography-high resolution tandem mass spectrometry analysis coupled to a charged aerosol detector. After clustering the fractions based on chemical similarity, we performed free sensory analysis and classical descriptive analysis on each cluster. Our results confirmed the attribution of bitterness to iridoids and highlighted the role of other important compounds in the overall taste. This method provides a systematic approach for analyzing and potentially enhancing the taste profiles of plant-based beverages.

PMID:40330506 | PMC:PMC12051061 | DOI:10.1016/j.crfs.2025.101043

Categories: Literature Watch

Self-sustained rhythmic behavior of <em>Synechocystis</em> sp. PCC 6803 under continuous light conditions in the absence of light-dark entrainment

Wed, 2025-05-07 06:00

PNAS Nexus. 2025 Apr 25;4(5):pgaf120. doi: 10.1093/pnasnexus/pgaf120. eCollection 2025 May.

ABSTRACT

Circadian clocks regulate biological activities, providing organisms with a fitness advantage under diurnal conditions by enabling anticipation and adaptation to recurring external changes. Three proteins, KaiA, KaiB, and KaiC, constitute the circadian clock in the cyanobacterial model Synechococcus elongatus PCC 7942. Several techniques established to measure circadian output in Synechococcus yielded comparably weak signals in Synechocystis sp. PCC 6803, a strain important for biotechnological applications. We applied an approach that does not require genetic modifications to monitor the circadian rhythms in Synechococcus and Synechocystis. We placed batch cultures in shake flasks on a sensor detecting backscattered light via noninvasive online measurements. Backscattering oscillated with a period of ∼24 h around the average growth. Wavelet and Fourier transformations are applied to determine the period's significance and length. In Synechocystis, oscillations fulfilled the circadian criteria of temperature compensation and entrainment by external stimuli. Remarkably, dilution alone synchronized oscillations. Western blotting revealed that the backscatter was ∼6.5 h phase-delayed in comparison to KaiC3 phosphorylation.

PMID:40330109 | PMC:PMC12053491 | DOI:10.1093/pnasnexus/pgaf120

Categories: Literature Watch

Microbiome and Microbial Profiling of Arctic Snow Using Whole Genome Sequencing, Psychrophilic Culturing, and Novel Sampling Techniques

Wed, 2025-05-07 06:00

J Biomol Tech. 2025 Mar 24;36(1):3fc1f5fe.0f37be73. doi: 10.7171/3fc1f5fe.0f37be73. eCollection 2025 Apr 30.

ABSTRACT

Recent advances in massively parallel DNA sequencing have enabled researchers to study new areas of extreme environments. Of particular interest to many researchers are areas of the Arctic that have yet to be comprehensively examined using DNA techniques. These modern approaches to microbial profiling provide new critical data on systems biology not yet seen before from Arctic samples. The discovery of new microbes, microbial biochemical pathways, and biosynthetic gene clusters are critically important when characterizing the Arctic snow microbiome and can provide insights to discovering valuable biosynthetic gene clusters. In this study, 2 L of snow was collected from 15 sites 12 km east outside of Ilulissat, Greenland, using DNA-free sterile techniques. Snow was allowed to melt and immediately concentrated using the InnovaPrep CP sample concentrator. Whole genome DNA sequencing was performed on extracts using both Illumina and Nanopore sequencing as well as psychrophilic culturing. Individual cultures were also sequenced to determine whole genome content and species identity. The results showed a wide-ranging microbiome across the snow fields, including bacteria, yeast, and fungi, with Granulicella, Methylobabcterium, Nostoc, Sphingomonas, and Streptomyces being consistently detected at higher levels across the majority of sites and sequencing platforms, while Belnapia, Chlorogloea, Hymenobacter, Mesorhizobium, Narcardioides, Pseudomonas, Pseudonocardia, Roseomonas, and Solirubrobacter at comparatively lower abundances. The results of culture data for snow sites reveal Pseudomanas sp., Pseudomonas fluorescens Group, unknown Microbacteriaceae sp., Variovorax sp., Robbsia andropogonis, and low concentrations of Aureobasidium sp., Stylodothis sp., Sphingomonas sp., Hymenobacter sp., Caballeronia sordidicola, and two unknown species of yeast and one unknown species of bacteria.

PMID:40329984 | PMC:PMC12051450 | DOI:10.7171/3fc1f5fe.0f37be73

Categories: Literature Watch

De Novo Reconstruction of 3D Human Facial Images from DNA Sequence

Wed, 2025-05-07 06:00

Adv Sci (Weinh). 2025 May 7:e2414507. doi: 10.1002/advs.202414507. Online ahead of print.

ABSTRACT

Facial morphology is a distinctive biometric marker, offering invaluable insights into personal identity, especially in forensic science. In the context of high-throughput sequencing, the reconstruction of 3D human facial images from DNA is becoming a revolutionary approach for identifying individuals based on unknown biological specimens. Inspired by artificial intelligence techniques in text-to-image synthesis, it proposes Difface, a multi-modality model designed to reconstruct 3D facial images only from DNA. Specifically, Difface first utilizes a transformer and a spiral convolution network to map high-dimensional Single Nucleotide Polymorphisms and 3D facial images to the same low-dimensional features, respectively, while establishing the association between both modalities in the latent features in a contrastive manner; and then incorporates a diffusion model to reconstruct facial structures from the characteristics of SNPs. Applying Difface to the Han Chinese database with 9,674 paired SNP phenotypes and 3D facial images demonstrates excellent performance in DNA-to-3D image alignment and reconstruction and characterizes the individual genomics. Also, including phenotype information in Difface further improves the quality of 3D reconstruction, i.e. Difface can generate 3D facial images of individuals solely from their DNA data, projecting their appearance at various future ages. This work represents pioneer research in de novo generating human facial images from individual genomics information.

PMID:40329800 | DOI:10.1002/advs.202414507

Categories: Literature Watch

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