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PubMed1977

[Chromatin fibril. Structure and relationship to the nuclear membrane].

Literature for the recent years on chromatin fibrilla structure is reviewed in the work. Ultrastructural and molecular organization of the elementary chromatin subunits--nucleosomes, discovered in 1974 is discussed and their relation to other discrete chromatin particles is analyzed. The author represents his own data on electron microscopic studies of the cell nucleus after certain experimental effect demonstrating a complex structure of chromatin particles. The scheme of chromatin fibrilla structure is given; morphologic and functional aspects of its connection with the nuclear membrane are considered.

Animals↗

PubMed2026

From glycosylation to inflammation: insights from NMR-Derived GlycA and GlycB.

Post-translational modifications (PTMs) play a crucial role in increasing proteomic diversity. N-linked glycosylation acts as a key regulatory layer that influences protein stability, trafficking, circulation, and immune responses. Unlike conventional inflammatory biomarkers that measure individual proteins, nuclear magnetic resonance (NMR) spectroscopy identifies the combined signals GlycA and GlycB from glycoproteins, offering an overall view of systemic glycoprotein changes. These signals represent the N-glycosylation patterns of several abundant acute-phase proteins (APPs), giving detailed molecular insights. This review offers a detailed assessment of GlycA and GlycB as mechanistically grounded indicators of liver glycoprotein remodeling and systemic inflammation. GlycA mainly indicates the levels and structural complexity of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) residues linked to acute-phase glycoproteins and glycan branching. In contrast, GlycB reflects changes in terminal sialylation, which influences glycoprotein half-life, immune recognition via lectins, and inflammatory signaling. Collectively, these biomarkers combine measurements of hepatic APP production with variations in glycan structure, offering mechanistically anchored reporters of hepatic glycoprotein remodeling. We explore the enzymatic pathways responsible for N-glycan branching, fucosylation, and sialylation, as well as the roles of major APP scaffolds in the GlycA and GlycB resonances. We also highlight the emerging clinical significance of these signals across infectious, autoimmune, cardiovascular, metabolic, neurodegenerative, and cancer-related diseases. Rather than serving simply as markers of inflammation, GlycA and GlycB provide mechanistically interpretable readouts of cytokine-driven hepatic glycoprotein remodeling and systemic immune activation, supporting their application in disease risk stratification, longitudinal monitoring, therapeutic response assessment, and precision medicine.

GlycA↗

PubMed1979

Structure of the D-mannan and D-arabino-D-galactan in Crithidia fasciculata: changes in proportion with age of culture.

Cells of the insect flagellate Crithidia fasciculata contained mannan and arabinogalactan components, whose porportion varied with culture age, the former predominating during early stages, and the latter during the later stages of exponential growth and the deceleration phase. The mannan was a beta-D-(1 leads to 2)-linked D-mannopyranan. The arabinogalactan had a complex structure containing, in part, a beta-D-(1 leads to 3)-linked galactopyranose main-chain substituted in the 2 positions by single-unit D-arabinopyranose side-chains and with some unsubstituted units.

Animals↗

PubMed2025

CS Ratio is an immune-related prognostic biomarker for cervical cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in cancer progression but its complex structure significant variability among patients present considerable challenges for research. Recent studies have demonstrated that macrophage polarization states defined by the expression levels of CXCL9 SPP1 (CS Ratio) are more prognostically relevant than traditional M1/M2 markers. The CS polarization state reflects a highly coordinated network of pro-tumor anti-tumor variables offering a simplified yet effective immune response indicator for the complex TME. The CS Ratio has been shown to correlate with the abundance of anti-tumor immune cells the gene expression programs of tumor-infiltrating cells responses to immunotherapy. Cervical cancer, one of the most common gynecological malignancies, still faces limited therapeutic options. CXCL9, a member of the CXC chemokine family, plays a critical role in immune regulation, inflammation, tumor growth, angiogenesis, and metastasis. Similarly, SPP1, a cytokine, influences immune-related pathways by regulating molecules such as interferon-γ and interleukin-12. However, no studies have systematically investigated the role of the CS Ratio in cervical cancer or its relationship with immunotherapy characteristics. Research in this area could provide critical insights into the role and clinical potential of the CS Ratio in cervical cancer and related tumors. METHODS: The expression ratio of CXCL9 to SPP1 was analyzed in cervical cancer patients using data from the Gene Expression Omnibus (GEO) database, which revealed significant differences. Data for cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. The optimal cutoff value for the CS Ratio was determined using the maxstat package in R, and Kaplan-Meier (KM) survival curves were constructed. Patients were categorized into High and Low groups based on the median CS Ratio. Immune scores were analyzed, and immune cell infiltration was assessed using CIBERSORT. Differences in the CS Ratio were evaluated across patients with varying pathological T stages and FIGO stages. Additionally, receiver operating characteristic (ROC) analysis was performed using the pROC package in R to calculate the area under the curve (AUC). Univariate and multivariate Cox regression analyses were performed to evaluate the potential of the CS Ratio as an independent prognostic factor in cervical cancer. A Cox regression-based nomogram integrating four key features was subsequently developed for the TCGA-CESC cohort. Nomogram performance was assessed using calibration curves and ROC analysis. RESULTS: The CS Ratio was significantly lower in cervical cancer patients compared to normal controls (P < 0.05). KM survival curves indicated that patients in the CS High group exhibited better prognoses. Immune score analysis revealed significantly higher immune scores (P < 0.05) and lower tumor purity (P < 0.05)in the CS High group compared to the Low group. CIBERSORT analysis revealed significantly higher proportions of CD8+ T cells (P < 0.05) and M1 macrophages (P < 0.05), and a significantly lower proportion of M2 macrophages (P < 0.05), in the CS High group compared to the Low group. The CS Ratio significantly decreased with advancing FIGO stage (P < 0.05). Both univariate (P < 0.05) and multivariate Cox regression analyses (P < 0.05) confirmed the CS Ratio as an independent prognostic factor. ROC analysis demonstrated that the CS Ratio had higher AUC values for predicting 1-year (AUC=0.69), 3-year (AUC=0.66), and 5-year OS (AUC=0.68) than CXCL9 or SPP1 alone. The Cox regression-based nomogram integrating four key features demonstrated predictive capability for 1-, 3-, and 5-year OS in CESC patients (Concordance Index = 0.751; 95% CI: 0.678-0.824; p = 1.50Í10-11). Significant survival differences were observed between the high-risk and low-risk groups based on the nomogram score. ROC analysis yielded high AUC values for survival prediction: 0.85 (95% CI: 0.94-0.75) at 1-year, 0.74 (95% CI:0.84-0.64) at 3-year, and 0.72 (95% CI:0.84-0.61) at 5-year. CONCLUSION: The CS Ratio may serve as a more effective prognostic biomarker for cervical cancer patients.

CXCL9↗

PubMed2026

PangyPlot: multi-scale interactive visualization of pangenome variation graphs.

SUMMARY: Pangenome variation graphs integrate multiple samples into a unified representation, mitigating the reference bias inherent to linear genomes. However, these graphs can be large and structurally complex. Existing visualization tools are each confined to a fixed scale of resolution, requiring researchers to switch between multiple tools to examine variation at different levels of detail. PangyPlot is an interactive pangenome browser designed for multi-scale exploration of reference variation graphs from full chromosome to nucleotide-level sequence segments. PangyPlot anchors navigation to linear reference coordinates, organizes variation into hierarchical bubble structures, and uses a force-directed layout engine for automatic node arrangement. AVAILABILITY AND IMPLEMENTATION: An instance preloaded with data is available at https://pangyplot.research.sickkids.ca. Source code and documentation are openly available at https://github.com/strug-hub/pangyplot under the MIT License.

Software↗

PubMedDate not supplied

[Characteristics of phages of spore-forming bacteria isolated from the soil].

Phages lyzing spore forming bacteria were isolated from soil, and their biological properties and fine structure were studied. The spectrum of lytic activity was determined as well as parameters of the intracellular phage growth. The burst size of the phage varies from 8 to 725 particles per infected cell, the latent period lasts 25-100 min for various phages. According to the data of electron microscopy, the phages are divided into three morphological groups. The phages Tg7, AR13 and BPP10 have a complex structure.

Bacillus subtilis↗

PubMed1976

Recognition and classification of structure by means of stereological methods in neurobiology.

The problem of measuring fine structure of individual particles without losing information on largescale characteristics of particle arrangement is discussed. With the help of stereological and pattern recognition methods a possible solution of this important problem is introduced. The domain specimen for which the brain serves as an example is characterized by two main properties. One of them being the position dependent 'aggregate characteristics' (distribution of neurons within the specimen), the other position invariant 'single cell characteristics' (structural properties of single neurons). It is shown that by simultaneous observation both properties together cannot be detected with sufficient accuracy by conventional methods. This is the decisive problem of 'correlation microscopy'. The method described in this paper is based on selection of the most informative variables and selection of subdomains (e.g. sections and reference planes). This results in a very general probabilistic concept in modern stereology, offering solutions to complex structure classification problems in biology.

Brain↗

PubMed1977

Quantitative comparison of the amygdala in insectivores and primates.

Comparative architectonic studies have resulted in a classification of the amygdaloid complex which differs somewhat from the commonly used classification (first proposed by Humphrey, 1936) by separating the cortical amygdaloid nucleus from the centromedial group and assigning it to the basolateral group, which then forms a cortico-basolateral group. The size changes of these groups and of the nucleus of the lateral olfactory tract (belonging to the centromedial group) and the large-celled part of the basal nucleus (belonging to the corticobasolateral group) have been investigated in representatives of an ascending primate scale. In all structural complexes investigated so far, the small-celled part of the cortico-basolateral group is the most progressive. In descending order of progression there follow: the corticobasolateral group as a whole, the amygdala as a whole, and the large-celled basal nucleus. No clear changes were found in the centromedial group as a whole, whereas the size of the nucleus of the lateral olfactory tract, which represents a small component of this latter group, shows a strong reduction. These differences in the developmental trends point to increasing or decreasing capacities of the functional (limbic and olfactory) systems, to which these structures are related.

Amygdala↗

PubMed2026

Integrating structure and experimental data annotations with computational modeling framework for predicting micro-nanoplastics toxicities.

The wide use of plastic materials leads to increased emissions of micro-nanoplastics (MNPs) into the environment, raising significant concerns about their impact on human health. Traditional experimental approaches for assessing MNPs toxicity are costly, time-consuming, and there are no experimental protocols that are universally acceptable. Computational modeling using machine learning (ML) approaches provides an efficient alternative to MNP toxicity assessment. However, most modeling studies of MNPs are limited due to the lack of high-quality data and there are few previous modeling studies considering complex structures of MNPs for model training. To address this challenge, we constructed three MNP datasets with popular toxicity endpoints from various resources and used nanostructure annotation techniques to create virtual MNPs (vMNPs) for all MNP structures. The MNP structures were digitalized from annotated vMNPs, and geometrical descriptors were calculated using the Delaunay Tessellation approach. Moreover, important experimental information, such as concentrations and cell lines, were transformed into extra training variables. Partial least squares regression (PLSR) models were built using both experimental and geometrical descriptors and validated through a leave-one-out cross validation procedure. The resulting models showed reasonable performance in predicting toxicity potentials of MNPs for the three endpoints in the present datasets. Moreover, an additional library of vMNPs with their predicted properties and bioactivities was constructed, directing further research of new MNPs. This study provides three novel ML models for MNPs by integrating geometrical and experimental descriptors, which have the potential to assess new MNPs for their toxicity. The modeling strategy developed in this study can be easily expanded to model other MNP toxicity endpoints and create promising new models for MNP toxicity assessments.

Data annotation↗

PubMed2025

Proximity Labeling of Cell Surface Proteins via Cell Surface Remodeling.

Within the complex interplay of proteins, lipids and carbohydrates at the cell surface is the surfaceome, a dense layer of proteins and their posttranslationally modified counterparts that serves as a hub for cell signaling and signal transduction. The surfaceome plays crucial roles in mediating interactions between cells and the extracellular environment, which combined with their availability at the cell surface make it an attractive therapeutic target. Despite its importance, the development of technologies to selectively target cell surface proteins for empirical identification is challenged by their structural complexity. Here, we describe a proximity labeling-based technique to covalently label proteins at the cell surface with a biotin handle, enabling downstream streptavidin-based enrichment and manipulation in a variety of modalities, including fluorescence imaging, western blotting, and mass spectrometry-based proteomics.

Membrane Proteins↗

PubMed2026

Two melanic pigment patterns are associated with a sex chromosome-linked oncogene in the mountain swordtail Xiphophorus nezahualcoyotl.

Sex-linked traits are widespread, but their genetic architecture has been challenging to characterize, due in part to the repetitive and structurally complex nature of sex chromosomes. In swordtails and platyfish of the genus Xiphophorus, diverse melanic pigmentation patterns are thought to be controlled by a region on the sex chromosomes classically referred to as the "macromelanophore determining locus". Despite nearly a century of study, the identity of the causal gene remains controversial, partially due to previous inability to fully sequence the sex chromosomes. Here, we characterize and investigate two melanin-based pigmentation phenotypes in the species X. nezahualcoyotl: "spotted side" and "marmoratus". We generate a gapless near-telomere-to-telomere X. nezahualcoyotl assembly and perform GWAS to identify regions associated with pigmentation pattern variation and sex-determination. We find both patterns map near the sex-determining region and to a narrow interval near the oncogene xmrk. By generating additional long-read assemblies of sex chromosomes derived from individuals with distinct phenotypes, we find haplotypes containing xmrk can be both X- and Y-linked, and vary dramatically in gene content, structure, and accumulation of repetitive elements including a newly described composite satellite. This variability may impact the region's stability and affect recombination between haplotypes associated with each pattern. Our results shed light on a longstanding debate surrounding the genetic architecture of sex-linked phenotypes. More generally, we showcase how long-read sequencing can reveal phenotypic variation linked to complex and dynamic genomic regions, which may contribute to the evolution of diverse sex-linked traits.

Journal Article↗

PubMed1979

Comparative cytology of hydrochloric acid secreting cells.

A comparative study of the oxyntic cells of the stomach of Vertebrates is presented. A system of membranous tubules which is apparently inter-convertible with the luminal plasma membrane is described as an important structural feature in all classes. In all Vertebrates with the sole exception of Mammals, this system shares a common cell with the structures involved in the secretion of zymogen. In Mammals it becomes segregated into a specialized cell type, the parietal cell, characterized in addition by the presence of a long tortuous intracellular canaliculus, which serves as its secretory pole. The hypothesis is presented and discussed that the parietal cell is capable of achieving a higher efficiency in hydrochloric acid secretion by the existence of the intracellular canaliculus which makes the immediate surroundings of the secretory pole independent of the contents of the gastic lumen. In Birds (whose gastric glands do not possess parietal cells) a corresponding effect can be achieved only by complex structures such as the compound gastric glands. An explanation is hereby offered for the unique features of the Avian stomach.

Amphibians↗

PubMed1976

Function of gene 49 of bacteriophage T4. II. Analysis of intracellular development and the structure of very fast-sedimenting DNA.

With the exception of mutants in gene 49, all mutants in phage T4 defective in the process of head filling accumulate a normal replicative DNA intermediate of 200S. Mutants in gene 49 produce a very fast-sedimenting (VFS) DNA with s values of greater than 1,000S. The intracellular development of the VFS-DNA generated in gene 49-defective phage-infected cells was followed by sedimentation analysis of crude lysates on neutral sucrose gradients. It was observed that the production of a 200S replicative intermediate is one step in the development of VFS-DNA. After restoring permissive conditions the development of the VFS-DNA can be reversed, but the 200S form is not regenerated under these conditions. The process of head filling can take place from the VFS-DNA under permissive conditions. From the absence of other components in the VFS-DNA complexes, its high resistance to shearing, its resistance against the attack of the single-strand-specific nuclease S1, and from its appearance in the electron microscope, a complex structure of tightly packed DNA is inferred. The demonstration by the electron microscope of branched DNA structures sometimes closely related to partially filled heads is taken in support of the idea that the process of head filling in gene 49-defective phage-infected cells is blocked by some steric hindrance in the DNA. In light of these results, the role of gene 49 is discussed as a control function for the clearance of these structures. A fixation procedure for cross-linking of gene 49-defective heads to the VFS-DNA allowed us to study progressive stages in the process of head filling. Electron microscopic evidence is presented which suggests that during the initial events the DNA accumulates in the vertexes of the head.

Cell Membrane↗

PubMed2026

Co-option of stomata in the convergent evolution of fern nectaries.

Understanding the origin of new structures is a central goal of evolutionary biology. In many instances, novel phenotypes arise through heterotopy: the expression of a structure in a new location. Using bracken fern (Pteridium aquilinum) as a model, we combine genomics, transcriptomics and metabolomics to begin to explore the origin and developmental routes in the convergent evolution of ant-enticing nectaries. We observe that P. aquilinum does not exclusively express flowering plant 'nectary genes' during nectary development. Rather, this fern builds nectaries through co-option of stomata. Specifically, P. aquilinum heterotopically expresses canonical angiosperm stomatal regulatory genes, leading to stomatal development in novel positions along the petiole. These non-laminar stomata were co-opted for nectar secretion through the expression of putative sugar transport genes, forming secretory nectarostomata. This work provides two advances in our understanding of nectary evolution and the origin of complex structures. First, heterotopic expression of stomata, and later exaptation, represents one realized developmental mechanism for the evolution of nectar glands. Second, while there are many routes to nectary evolution, nectarostomata development is a repeatable path that has evolved in ferns and flowering plants, representing an impressive case of convergent evolution through the same developmental mechanism, despite over 400 million years of divergent history.

Plant Stomata↗

PubMed1978

Freeze-fracture identification of sterol-digitonin complexes in cell and liposome membranes.

To advance our understanding of the organization of cholesterol within cell membranes, we used digitonin in freeze-fracture investigations of model lipid vesicles and tissues. Cholesterol suspensions or multilamellar liposomes composed of phosphatidylcholine with and without cholesterol were exposed to digitonin. Freeze-fracture replicas of those multilamellar liposomes containing cholesterol displayed either 50--60-nm wide intramembrane corrugations or extramembrane tubular complexes. Comparable intramembrane hemitubular scallops and extra-cellular free tubular complexes were observed in thin sections. Exposure of sperm, erythrocytes (whole and ghosts), and intact tissues (skin, liver, adrenal gland, epididymis) to digitonin produced the same types of intra- and extramembrane complexes or furrows as were formed in liposomes. The plasma membrane of guinea pig serum tail had two unfurrowed regions: the annulus and the zipper. Incubating erythrocyte membranes with digitonin resulted in rapid displacement of cholesterol, accompanied by intramembrane particle clustering and membrane faceting, a feature which we did not see in the intact epithelia studied. In freeze-fractured epithelia, we found that plasma membranes, lysosomes, and some vesicular organelles commonly furrowed, but that mitochondrial membranes and nuclear envelopes were generally spared, correlating well with their known cholesterol content. Finally, plasma membrane corrugations approached but did not impinge on either gap or tight junctions, or on coated vesicles. We conclude that freeze-fracture of membranes exposed to digitonin: (a) reveals distinctive cholesterol-digitonin structural complexes; (b) distinguishes cholesterol-rich and -poor organelle membranes; and (c) demonstrates membrane domains rich or poor in cholesterol.

Adrenal Glands↗

PubMed2024

Nanobodies: From High-Throughput Identification to Therapeutic Development.

The camelid single-domain antibody fragment, commonly referred to as a nanobody, achieves the targeting power of conventional monoclonal antibodies (mAbs) at only a fraction of their size. Isolated from camelid species (including llamas, alpacas, and camels), their small size at ∼15 kDa, low structural complexity, and high stability compared with conventional antibodies have propelled nanobody technology into the limelight of biologic development. Nanobodies are proving themselves to be a potent complement to traditional mAb therapies, showing success in the treatment of, for example, autoimmune diseases and cancer, and more recently as therapeutic options to treat infectious diseases caused by rapidly evolving biological targets such as the SARS-CoV-2 virus. This review highlights the benefits of applying a proteomic approach to identify diverse nanobody sequences against a single antigen. This proteomic approach coupled with conventional yeast/phage display methods enables the production of highly diverse repertoires of nanobodies able to bind the vast epitope landscape of an antigen, with epitope sampling surpassing that of mAbs. Additionally, we aim to highlight recent findings illuminating the structural attributes of nanobodies that make them particularly amenable to comprehensive antigen sampling and to synergistic activity-underscoring the powerful advantage of acquiring a large, diverse nanobody repertoire against a single antigen. Lastly, we highlight the efforts being made in the clinical development of nanobodies, which have great potential as powerful diagnostic reagents and treatment options, especially when targeting infectious disease agents.

Animals↗

PubMed2026

Relative Quantitative Analysis of Site-Specific N-Linked Glycosylation in Hyperglycosylated Interferon-β via Mass Spectrometry.

Glycosylation is a critical determinant of the efficacy, stability, and pharmacological behavior of therapeutic proteins. R27T, an engineered variant of interferon-β1a, contains two N-glycosylation sites (Asn25 and Asn80), increasing its structural complexity and analytical requirements. In this study, we performed comprehensive total and site-specific glycan profiling of R27T using complementary analytical approaches. For total glycan analysis, the released N-glycans were fluorescently labeled with procainamide, providing enhanced sensitivity and broader glycan coverage compared with conventional 2-aminobenzamide labeling. Site-specific glycan profiling was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based peptide mapping. Protease digestion conditions were optimized to improve recovery of site-specific glycopeptides, with chymotrypsin identified as the most effective enzyme for resolving glycopeptides from individual glycosylation sites. Total glycan distributions reconstructed from peptide-mapping data were compared with fluorescence-based glycan profiling, showing that total and site-specific glycan data can be effectively combined. Minor discrepancies were observed depending on glycan structure, mainly due to differences in ionization efficiency. Distinct glycan distributions were observed between the two N-glycosylation sites of R27T. Molecular modeling further suggested that the additional glycan at Asn25 may enhance structural stability and receptor-binding affinity. These results demonstrate an integrative strategy for accurate glycan characterization in multi-site glycoproteins relevant to biotherapeutic development.

Glycosylation↗

PubMed2026

Chromosome-scale genome remodeling in tumor evolution: Copy number alterations and structural variants as two sides of the same coin.

Chromosome-scale genomic rearrangements are a dominant force in tumor evolution. Copy-number alterations (CNAs) and structural variants (SVs) constitute two complementary axes of this process. Although detection technologies now deliver near-comprehensive catalogs, technical resolution has outpaced conceptual integration. In this review, we frame CNAs and SVs as inextricable facets of chromosomal aberrations. They reshape cancer genomes through altered gene dosage and three-dimensional regulatory rewiring. CNAs quantify the gene-dosage imbalance, yet arise through mechanistically distinct routes. Segmental CNAs typically require chromosomal breakage, and therefore often coincide with SV junctions. By contrast, whole-chromosome aneuploidy and whole-genome doubling (WGD) primarily reflect mitotic or cytokinetic failure and can occur without local breakpoints, while nevertheless reshaping the karyotypic landscape and seeding subsequent structural complexity. SVs, in turn, range from unbalanced events that alter copy number to ostensibly balanced exchanges that predominantly rewire regulatory architecture. Despite their diverse and sometimes catastrophic architectures, SVs are ultimately rooted in double-strand break formation and error-prone resolution. By integrating CNAs and SVs within a unified mechanistic and functional framework, we aim to convert catalogs into concepts and distill the organizing principles that govern tumor genome evolution.

Humans↗